257
Views
88
CrossRef citations to date
0
Altmetric
Miscellaneous

Mechanisms of tumour invasion and metastasis: emerging targets for therapy

&
Pages 217-233 | Published online: 25 Feb 2005

Bibliography

  • SCHIRRMACHER V: Cancer metastasis: experimental approaches, theoretical concepts, and impacts for treatment strategies. Adv. Cancer Res. (1985) 43:1–73.
  • PRICE JT, BONOVICH MT, KOHN EC: The biochemistry of cancer dissemination. Grit. Rev Biochern. Mal Biol. (1997) 32:175–253.
  • LIOTTA LA, STETLER-STEVENSON WG, STEEG PS: Cancer invasion and metastasis: positive and negative regulatory elements. Cancer Invest. (1991) 9:543–551.
  • KOHN EC, LIOTTA LA: Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res. (1995) 55:1856–1862.
  • TIMPL R, BROWN JC: Supramolecular assembly of basement membranes. Bioessays (1996) 18:123–132.
  • BISSELL MJ, WEAVER VM, LELIEVRE SA, WANG F, PETERSEN OW, SCHMEICHEL KL: Tissue structure, nuclear organization, and gene expression in normal and malignant breast. Cancer Res. (1999) 59:1757–1763.
  • PARK CC, BISSELL MJ, BARCELLOS-HOFF MH: The influence of the microenvironment on the malignant phenotype. Mal Med. Today (2000) 6:324–329.
  • LIOTTA LA, KOHN EC: The microenvironment of the tumour-host interface. Nature (2001) 411:375–379.
  • ••Comprehensive and current review on thesteps comprising the metastatic cascade.
  • ZETTER BR: Angiogenesis and tumor metastasis. Ann. Rev Med (1998) 49:407–424.
  • WERNERT N: The multiple roles of tumour stroma. Virchows Arch. (1997) 430:433–443.
  • COUSSENS LM, TINKLE CL, HANAHAN D, WERB Z: MMP-9 Supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell (2000) 103:481–490.
  • STERNLICHT MD, LOCHTER A, SYMPSON CJ et al.: The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell (1999) 98:137–146.
  • STERNLICHT MD, BISSELL MJ, WERB Z: The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter. Oricogerre (2000) 19:1102–1113.
  • AL-MEHDI AB, TOZAWA K, FISHER AB, SHIENTAG L, LEE A, MUSCHEL RJ: Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat. Med. (2000) 6:100–102.
  • DEMICHELI R: Tumour dormancy: findings and hypotheses from clinical research on breast cancer. Semi]. Cancer Biol. (2001) 11:297–306.
  • GIANCOTTI FG, RUOSLAHTI E: Integrin signaling. Science (1999) 285:1028–1032.
  • ••Comprehensive review on signaltransduction from integrins.
  • HYNES RO: Integrins: versatility, modulation, and signaling in cell adhesion. Cell (1992) 69:11–25.
  • VARNER JA, CHERESH DA: Integrins and cancer. Curr. Opin Cell Biol. (1996) 8:724–730.
  • HUMPHRIES MJ: Integrin cell adhesion receptors and the concept of agonism. Trends Pharmacol. Li. (2000) 21:29–32.
  • KEELY P, PARISE L, JULIANO R: Integrins and GTPases in tumour cell growth, motility and invasion. Trends Cell Biol. (1998) 8:101–106.
  • FRISCH SM, RUOSLAHTI E: Integrins and anoikis. Curr. Opin Cell Biol. (1997) 9:701–706.
  • RUOSLAHTI E, ENGVALL E: Integrins and vascular extracellular matrix assembly. Clin. Invest. (1997) 99:1149–1152.
  • BROOKS PC: Role of integrins in angiogenesis. Eur. j Cancer (1996) 32A:2423–2429.
  • FISHMAN DA, KEARNS A, CHILUKURI K et al.: Metastatic dissemination of human ovarian epithelial carcinoma is promoted by alpha2beta I-integrin-mediated interaction with type I collagen. Invasion Metastasis (1998) 18:15–26.
  • ELLERBROEK SM, FISHMAN DA, KEARNS AS, BAFETTI LM, STACK MS: Ovarian carcinoma regulation of matrix metalloproteinase-2 and membrane Type 1 matrix metalloproteinase through betel integrin. Cancer Res. (1999) 59:1635–1641.
  • DUMIN JA, DICKESON SK, STRICKERTP et al.: Pro-collagenase-1 (matrix metalloproteinase-1) binds the alpha(2)beta(1) integrin upon release from keratinocytes migrating on type I collagen. Biol. Chem. (2001) 276:29368–29374.
  • RIIKONEN T, WESTERMARCK J, KOIVISTO L, BROBERG A, KAHARI VM, HEINO J: Integrin alpha 2 beta 1 is a positive regulator of collagenase (MMP-1) and collagen alpha 1(I) gene expression. Biol. Chem. (1995) 270:13548–13552.
  • STRICKER TP DUMIN JA, DICKESON SK et al.: Structural analysis of the alpha(2) integrin I domain/procollagenase-1 (matrix metalloproteinase-1) interaction. ..J. Biol. Chem. (2001) 276:29375–29381.
  • MATSUOKA T, YASHIRO M, NISHIMURA S et al.: Increased expression of alpha2betal-integrin in the peritoneal dissemination of human gastric carcinoma. Int.j Md. Med. (2000) 5:21–25.
  • ZUTTER MM, SANTORO SA, STAATZ WD, TSUNG YL: Re-expression of the alpha 2 beta 1 integrin abrogates the malignant phenotype of breast carcinoma cells. Proc. Nati Acad. Li. USA (1995) 92:7411–7415.
  • KEELY PJ, FONG AM, ZUTTER MM, SANTORO SA: Alteration of collagen-dependent adhesion, motility, and morphogenesis by the expression of antisense alpha 2 integrin mRNA in mammary cells. I Cell Sci. (1995) 108:595–607.
  • TANAKA Y, MIMORI K, SHIRAISHI T et al.: Alpha6 integrin expression in esophageal carcinoma. Int. I Oncol. (2000) 16:725–729.
  • FRIEDRICHS K, RUIZ E FRANKE F, GILLE I, TERPE HJ, IMHOF BA: High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival. Cancer Res. (1995) 55:901–906.
  • MUKHOPADHYAY R, THERIAULT RL, PRICE JE: Increased levels of alpha6 integrins are associated with the metastatic phenotype of human breast cancer cells. Clin Exp. Metastasis (1999) 17:325–332.
  • VOGELMANN R, KREUSER ED, ADLER G, LUTZ MP: Integrin alpha6betal role in metastatic behavior of human pancreatic carcinoma cells. Int. Cancer (1999) 80:791–795.
  • TAGLIABUE E, GHIRELLI C, SQUICCIARINI P, AIELLO P, COLNAGHI MI, MENARD S: Prognostic value of alpha6beta4 integrin expression in breast carcinomas is affected by laminin production from tumor cells. Clin. Cancer Res. (1998) 4:407–410.
  • BLOOD CH, ZETTER BR: Laminin regulates a tumor cell chemotaxis receptor through the laminin-binding integrin subunit alpha 6. Cancer Res. (1993) 53:2661–2666.
  • RUIZ P, DUNON D, SONNENBERG A, IMHOF BA: Suppression of mouse melanoma metastasis by EA-1, a monoclonal antibody specific for alpha 6 integrins. Cell Adhes. Commun. (1993) 1:67–81.
  • CARLONI V, MAZZOCCA A, PANTALEO P, CORDELLA C, LAFFI G, GENTILINI P: The integrin, alpha6betal, is necessary for the matrix-dependent activation of FAK and MAP kinase and the migration of human hepatocarcinoma cells. Hepatology (2001) 34:42–49.
  • HANGAN D, MORRIS VL, BOETERS L, VON BALLESTREM C, UNIYAL S, CHAN BM: An epitope on VLA-6 (alpha6betal) integrin involved in migration but not adhesion is required for extravasation of murine melanoma B16F1 cells in liver. Cancer Res. (1997) 57:3812–3817.
  • RABINOVITZ I, MERCURIO AM: The integrin alpha6beta4 functions in carcinoma cell migration on laminin-1 by mediating the formation and stabilization of actin-containing motility structures. I Cell Biol. (1997) 139:1873–1884.
  • SHAW LM: Identification of insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the alpha6beta4 integrin-dependent activation of phosphoinositide 3-0H kinase and promotion of invasion. Ma. Cell. Biol. (2001) 21:5082–5093.
  • TRUSOLINO L, BERTOTTI A, COMOGLIO PM: A signaling adapter function for alpha6beta4 integrin in the control of HGF-dependent invasive growth. Cell (2001) 107:643–654.
  • ••Seminal paper showing the firstdemonstration of adapter function for a6p4.
  • BREUSS JM, GALLO J, DELISSER HM et al.: Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. I Cell Sci. (1995) 108:2241–2251.
  • AGREZ M, GU X, TURTON J et al.: Thealphavbeta6 integrin induces gelatinase B secretion in colon cancer cells. Int. j Cancer (1999) 81:90–97.
  • THOMAS GJ, LEWIS ME HART IR, MARSHALL JF, SPEIGHT PM: Alphavbeta6 integrin promotes invasion of squamous carcinoma cells through up-regulation of matrix metalloproteinase-9. Intl Cancer (2001) 92:641–650.
  • MUNGER JS, HUANG X, KAWAKATSU H et al.: The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell (1999) 96:319–328.
  • •Identifies novel function for avP6 integrin.
  • WONG SF, LAI LC: The role of TGFIDeta in human cancers. Pathology (2001) 33:85–92.
  • DUMONT N, ARTEAGA CL: Transforming growth factor-beta and breast cancer: tumor promoting effects of transforming growth factor-beta. Breast Cancer Res. (2000) 2:125–132.
  • PASCHE B: Role of transforming growthfactor beta in cancer. j Cell. Physiol. (2001) 186:153–168.
  • MILLER WH, KEENAN RIVI, WILLETTE RN, LARK MW: Identification and in vivo efficacy of small-molecule antagonists of integrin alphavbeta3 (the vitronectin receptor). Drug Disc. Today (2000) 5:397–408.
  • ••Comprehensive review of small moleculestargetting avil3, many in clinical trial.
  • MARSHALL JE HART IR: The role of alpha v-integrins in tumour progression and metastasis. &min. Cancer Biol. (1996) 7:129–138.
  • NIP J, BRODT P: The role of the integrinvitronectin receptor, alphavbeta3 in melanoma metastasis. Cancer Metastasis Rev (1995) 14:241–252.
  • BROOKS PC, STROMBLAD S, SANDERS LC et al.: Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell (1996) 85:683–693.
  • BROOKS PC, SILLETTI S, VON SCHALSCHA TL, FRIEDLANDER M, CHERESH DA: Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell (1998) 92:391–400.
  • •First demonstration of haemopexin fragment of 1\41\4P2 (PEX) inhibition of the MMP-2-binding capacity of avP3 integrin.
  • FELDING-HABERMANN B, MUELLER BM, ROMERDAHL CA, CHERESH DA: Involvement of integrin alpha V gene expression in human melanoma tumorigenicity. j Clin. Invest. (1992) 89:2018–2022.
  • FILARDO EJ, BROOKS PC, DEMING SL, DAMSKY C, CHERESH DA: Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo. J. Cell Biol. (1995) 130:441–450.
  • HSU MY, SHIH DT, MEIER FE etal.: Adenoviral gene transfer of beta3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma. Am. J Pathol. (1998) 153:1435–1442.
  • MONTGOMERY AM, REISFELD RA, CHERESH DA: Integrin alpha v beta 3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen. Proc. Nati Acad. Li. USA (1994) 91:8856–8860.
  • ZHENG DQ, WOODARD AS, FORNARO M, TALLINI G, LANGUINO LR: Prostatic carcinoma cell migration via alpha(v)beta3 integrin is modulated by a focal adhesion kinase pathway. Cancer Res. (1999) 59:1655–1664.
  • CLEMMONS DR, HORVITZ G, ENGLEMAN W, NICHOLS T, MORALEZ A, NICKOLS GA: Synthetic alphavbeta3 antagonists inhibit insulin-like growth factor-I-stimulated smooth muscle cell migration and replication. Endocrinology (1999) 140:4616–4621.
  • KERR JS, SLEE AM, MOUSA SA: Small molecule alpha(v) integrin antagonists: novel anticancer agents. Expert Opin. Investig. Drugs (2000) 9:1271–1279.
  • DERYUGINA El, RATNIKOV B, MONOSOV E etal.: MT1-MIVIP initiates activation of pro-MMP-2 and integrin alphav beta3 promotes maturation of MIV1P-2 in breast carcinoma cells. Exp. Cell Res. (2001) 263:209–223.
  • SILLETTI S, KESSLER T, GOLDBERG J, BOGER DL, CHERESH DA: Disruption of matrix metalloproteinase 2 binding to integrin alphavbeta3 by an organic molecule inhibits angiogenesis and tumor growth in vivo. Proc. Nati Acad. Li. USA (2001) 98:119–124.
  • ••Successful screening of low Mr compoundsto target MMP-2-binding of avP3 integrin.
  • GUTHEIL JC, CAMPBELL TN, PIERCE PR etal.: Targeted antiangiogenic therapy for cancer using vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Chia. Cancer Res. (2000) 6:3056-3061. avP3 integrin-targeted clinical trial against cancer.
  • POSEY JA, KHAZAELI MB, DELGROSSO A et al.: A pilot trial of vitaxin, a humanized anti-vitronectin receptor (anti alpha v beta 3) antibody in patients with metastatic cancer. Cancer Biother. Radiopharin. (2001) 16:125–132.
  • PATEL SR, JENKINS J, PAPADOPOLOUS N et al.: Pilot study of vitaxin-an angiogenesis inhibitor-in patients with advanced leiomyosarcomas. Cancer (2001) 92:1347–1348.
  • MARRS JA, NELSON WJ: Cadherin cell adhesion molecules in differentiation and embryogenesis. Int. Rev Cytol. (1996) 165:159–205.
  • PERL AK, WILGENBUS P, DAHL U, SEMB H, CHRISTOFORI G: A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature (1998) 392:190–193.
  • FRIXEN UH, BEHRENS J, SACHS M et al.: E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J. Cell Biol. (1991) 113:173–185.
  • MBALAVIELE G, DUNSTAN CR, SASAKI A, WILLIAMS PJ, MUNDY GR, YONEDA T: E-cadherin expression in human breast cancer cells suppresses the development of osteolytic bone metastases in an experimental metastasis model. Cancer Res. (1996) 56:4063–4070.
  • BIRCHMEIER W, BEHRENS J: Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochlin. Biophys. Acta (1994) 1198:11–26.
  • BRACKE ME, VAN ROY FM, MAREEL MM: The E-cadherinicatenin complex in invasion and metastasis. Curr. Top. Microbial. Inunurrol. (1996) 213:123–161.
  • ••Comprehensive review of E-cadherinimplications for invasion and metastasis.
  • BRAGA VM, MACHESKY LM, HALL A, HOTCHIN NA: The small GTPases Rho and Rac are required for the establishment of cadherin-dependent cell-cell contacts. Cell Biol. (1997) 137:1421–1431.
  • HORDIJK PL, TEN KLOOSTER JP, VAN DER KAMMEN RA, MICHIELS F, OOMEN LC, COLLARD JG: Inhibition of invasion of epithelial cells by Tiaml-Rac signaling. Science (1997) 278:1464–1466.
  • NOE V, FINGLETON B, JACOBS K et al.: Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. _J. Cell Sci. (2001) 114:111–118.
  • BECKER KF, ATKINSON MJ, REICH U et al.: E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. (1994) 54:3845–3852.
  • BERX G, CLETON-JANSEN AM, NOLLET F et al.: E-cadherin is a tumour/ invasion suppressor gene mutated in human lobular breast cancers. EMBO 1 (1995) 14:6107–6115.
  • RISINGER JI, BERCHUCK A, KOHLER MF, BOYD J: Mutations of the E-cadherin gene in human gynecologic cancers. Nat. Genet. (1994) 7:98–102.
  • SHIMAZUI T, SCHALKEN JA, GIROLDI LA et al.: Prognostic value of cadherin-associated molecules (alpha-, beta, and gamma-catenins and p120cas) in bladder tumors. Cancer Res. (1996) 56:4154–4158.
  • BEHRENS J, VON KRIES JP, KUHL M et al.: Functional interaction of beta-catenin with the transcription factor LEF-1. Nature (1996) 382:638–642.
  • MOLENAAR M, VAN DE WETERING M, OOSTERWEGEL M et al.: XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell (1996) 86:391–399.
  • MORIN PJ, SPARKS AB, KORINEK V et al.: Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science (1997) 275:1787–1790.
  • RUBINFELD B, ROBBINS P, EL-GAMIL M, ALBERT I, PORFIRI E, POLAKIS P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science (1997) 275:1790–1792.
  • MORIN PJ: Beta-catenin signaling and cancer. Bioessays (1999) 21:1021–1030.
  • ••Highlights the transcriptional regulationaspects of 13-catenin.
  • WONG SC, CHAN JK, LEE KC, HSIAO WL: Differential expression of p16/p21/ p27 and cyclin D1/D3, and their relationships to cell proliferation, apoptosis, and tumour progression in invasive ductal carcinoma of the breast. J. Patna. (2001) 194:35–42.
  • YU Q, GENG Y, SICINSKI P: Specific protection against breast cancers by cyclin D1 ablation. Nature (2001) 411:1017–1021.
  • UTSUNOMIYA T, DOKI Y, TAKEMOTO H et al.: Correlation of beta-catenin and cyclin D1 expression in colon cancers. Oncology (2001) 61:226–233.
  • NAKAYAMA S, SASAKI A, MESE H, ALCALDE RE, TSUJI T, MATSUMURA T: The E-cadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas. bit .j Cancer (2001) 93:667–673.
  • CORN PG, HEATH El, HEITMILLER Ret al.: Frequent hypermethylation of the 5' CpG island of E-cadherin in esophageal adenocarcinoma. Clin. Cancer Res. (2001) 7:2765–2769.
  • NOJIMA D, NAKAJIMA K, LI LC etal.: CpG methylation of promoter region inactivates E-cadherin gene in renal cell carcinoma. Ma. Carcinog. (2001) 32:19–27.
  • LI LC, ZHAO H, NAKAJIMA K et al.: Methylation of the E-cadherin gene promoter correlates with progression of prostate cancer. J. Ural. (2001) 166:705–709.
  • MENG Q, XU J, GOLDBERG ID, ROSEN EM, GREENWALD RA, FAN S: Influence of chemically modified tetracyclines on proliferation, invasion and migration properties of MDA-MB-468 human breast cancer cells. Clin. Exp. Metastasis (2000) 18:139–146.
  • MENG Q, GOLDBERG ID, ROSEN EM, FAN S: Inhibitory effects of indole-3-carbinol on invasion and migration in human breast cancer cells. Breast Cancer Res. Treat. (2000) 63:147–152.
  • ISLAM S, CAREY TE, WOLF GT, WHEELOCK MJ, JOHNSON KR: Expression of N-cadherin by human squamous carcinoma cells induces a scattered fibroblastic phenotype with disrupted cell-cell adhesion. J. Cell Biol. (1996) 135:1643–1654.
  • HAZAN RB, KANG L, WHOOLEY BP BORGEN PI: N-cadherin promotes adhesion between invasive breast cancer cells and the stroma. Cell Ac/lies. Commun. (1997) 4:399–411.
  • •First implications of N-cadherin in carcinoma progression.
  • NIEMAN MT, PRUDOFF RS, JOHNSON KR, WHEELOCK MJ: N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J. Cell Biol. (1999) 147:631–644.
  • HAZAN RB, PHILLIPS GR, QIAO RF, NORTON L, AARONSON SA: Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J. Cell Biol. (2000) 148:779–790.
  • STERNLICHT MD, WERB Z: How matrix metalloproteinases regulate cell behavior. Ann. Rev. Cell Dev. Biol. (2001) 17:463–516
  • ••Comprehensive review of both MMPbiochemistry, roles in cancer, and inhibition.
  • BRINCKERHOFF CE, RUTTER JL, BENBOW U: Interstitial collagenases as markers of tumor progression. Clin. Cancer Res. (2000) 6:4823–4830.
  • NOEL A, BOULAY A, KEBERS F et al.: Demonstration in viva that stromelysin-3 functions through its proteolytic activity. Oncogene (2000) 19: 1605-1612.
  • SATO H, SEIKI M: Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis. 1 Biochem. (Tokyo) (1996) 119:209–215.
  • NAKAHARA H, HOWARD L, THOMPSON EW et al.: Transmembrane/ cytoplasmic domain-mediated membrane Type 1-matrix metalloprotease docking to invadopodia is required for cell invasion. Proc. Nati Acad. Sci. USA (1997) 94:7959–7964.
  • HOLMBECK K, BIANCO P, CATERINA J etal.: MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell (1999) 99:81–92.
  • ZHOU Z, APTE SS, SOININEN R et al.: Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc. Nati Acad. Sci. USA (2000) 97:4052–4057.
  • ITOH T, TANIOKA M, YOSHIDA H, YOSHIOKA T, NISHIMOTO H, ITOHARA S: Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res. (1998) 58:1048–1051.
  • HOTARY K, ALLEN E, PUNTURIERI A, YANA I, WEISS SJ: Regulation of cell invasion and morphogenesis in a three-dimensional Type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3.1 Cell Biol. (2000) 149:1309–1323.
  • •Highlights the advantage of membrane-anchored MMPs over secreted MMPs.
  • HA HY, MOON HB, NAM MS etal.: Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice. Cancer Res. (2001) 61:984–990.
  • PULYAEVA H, BUENO J, POLETTE M et al.: MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells [published erratum appears in Clin. Exp. Metastasis (1997) 15 (3) :3381. Clin. Exp. Metastasis (1997) 15:111–120.
  • GILLES C, POLETTE M, PIETTE J etal.: High level of MT-MMP expression is associated with invasiveness of cervical cancer cells. Int. J. Cancer (1996) 65:209–213.
  • GILLES C, THOMPSON EW: The epithelial to mesenchymal transition and metastatic progression in carcinoma. Breast J. (1996) 2:83–96.
  • BECKETT RP: Recent advances in the field of matrix metalloproteinase inhibitors. (1996) 6:1305–1315.
  • ZUCKER S, CAO J, CHEN WT: Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene (2000) 19:6642–6650.
  • ••Comprehensive and candid appraisal ofclinical experiences with MMP-inhibitors.
  • SHALINSKY DR, BREKKEN J, ZOU H et al.: Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials. Ann. NY Acad. Li. (1999) 878:236–270.
  • NGUYEN M, ARKELL J, JACKSON CJ: Human endothelial gelatinases and angiogenesis. Intj Blocher)]. Cell Biol. (2001) 33:960–970.
  • THOMPSON EW, SLEDGE GW JR: Towards the therapeutic targeting of matrix metalloproteinases in breast cancer. In: Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics. Bowcock AM (Ed), Humanna Press, Totowa, NJ, USA (1999):437–452.
  • •Highlights the need for modified trial designs for MMP-inhibitors, and potentially other antimetastatic modalities.
  • WANG Y: The role and regulation of urokinase-type plasminogen activator receptor gene expression in cancer invasion and metastasis. Med. Res. Rev (2001) 21:146–170.
  • PLOUG M, RONNE E, BEHRENDT N, JENSEN AL, BLAST F, DANO K: Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. _J. Biol. Chem. (1991) 266:1926–1933.
  • CHAPMAN HA: Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration. Curr. Opin. Cell Biol. (1997) 9:714–724.
  • DECLERCK YA, LAUG WE: Cooperation between matrix metalloproteinases and the plasminogen activator-plasmin system in tumor progression. Enzyme Protein (1996) 49:72–84.
  • NALDINI L, TAMAGNONE L, VIGNA E et al.: Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor. EMBO J. (1992) 11:4825–4833.
  • ODEKON LE, BLAST F, RIFKIN DB: Requirement for receptor-bound urokinase in plasmin-dependent cellular conversion of latent TGF-beta to TGF-beta. J. Cell. Physiol. (1994) 158:398–407.
  • CHAPMAN HA, WET Y, SIMON DI, WALTZ DA: Role of urokinase receptor and caveolin in regulation of integrin signaling. Thromb. Haemost. (1999) 82:291–297.
  • KOSHELNICK Y, EHART M, STOCKINGER H, BINDER BR: Mechanisms of signaling through urokinase receptor and the cellular response. Thromb. Haemost. (1999) 82:305–311.
  • PREISSNER KT, KANSE SM, MAY AE: Urokinase receptor: a molecular organizer in cellular communication. Curr. Opin. Cell Biol. (2000) 12:621–628.
  • NGUYEN DH, CATLING AD, WEBB DJ et al.: Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J. Cell Biol. (1999) 146:149–164.
  • CROWLEY CW, COHEN RL, LUCAS BK, LIU G, SHUMAN MA, LEVINSON AD: Prevention of metastasis by inhibition of the urokinase receptor. Proc. Nati Acad. Li. USA (1993) 90:5021–5025.
  • LAKKA SS, RAJAGOPAL R, RAJAN MK et al.: Adenovirus-mediated antisense urokinase-type plasminogen activator receptor gene transfer reduces tumor cell invasion and metastasis in non-small cell lung cancer cell lines. CBI]. Cancer Res. (2001) 7:1087–1093.
  • WANG Y, LIANG X, WU S, MURRELL GA, DOE WF: Inhibition of colon cancer metastasis by a 3'- end antisense urokinase receptor mRNA in a nude mouse model. Int. J. Cancer (2001) 92:257–262.
  • PLOUG M, OSTERGAARD S, GARDSVOLL H et al.: Peptide-derived antagonists of the urokinase receptor. affinity maturation by combinatorial chemistry, identification of functional epitopes, and inhibitory effect on cancer cell intravasation. Biochemistry (2001) 40:12157–12168.
  • ••Derivation of rationally designedinhibitors of the urokinase receptor.
  • RIDLEY A: Molecular switches in metastasis. Nature (2000) 406:466–467.
  • HYNES NE, STERN DF: The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim. Biophys. Acta (1994) 1198:165–184.
  • SLAMON DJ, CLARK GM, WONG SG, LEVIN WJ, ULLRICH A, MCGUIRE WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science (1987) 235:177–182.
  • YU D, HUNG MC: Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene (2000) 19:6115–6121.
  • SPENCER KS, GRAUS-PORTA D, LENG J, HYNES NE, KLEMKE RL: ErbB2 is necessary for induction of carcinoma cell invasion by ErbB family receptor tyrosine kinases. J. Cell Biol. (2000) 148:385–397.
  • BRANDT BH, ROETGER A, DITTMAR T et al.: c-erbB-2/EGFR as dominant heterodimerization partners determine a motogenic phenotype in human breast cancer cells. FASEB J. (1999) 13:1939–1949.
  • ADAM L, VADLAMUDI R, KONDAPAKA SB, CHERNOFF J, MENDELSOHN J, KUMAR R: Heregulin regulates cytoskeletal reorganization and cell migration through the p21-activated kinase-1 via phosphatidylinosito1-3 kinase. I Biol. Chem. (1998) 273:28238–28246.
  • BURRIS HA 3RD: Docetaxel (Taxotere) in HER-2-positive patients and in combination with trastuzumab (Herceptin). Semi]. Oncol. (2000) 27:19–23.
  • STEBBING J, COPSON E, O'REILLY S: Herceptin (trastuzamab) in advanced breast cancer. Cancer Treat. Rev (2000) 26:287–290.
  • KAPELLER R, CANTLEY LC: Phosphatidylinositol 3-kinase. Bioessays (1994) 16:565–576.
  • RODRIGUEZ-VICIANA P, DOWNWARD J: Ras activation of phosphatidylinositol 3-kinase and Akt. Methods Lwow]. (2001) 333:37–44.
  • PRICE JT, TIGANIS T, AGARWAL A, DJAKIEW D, THOMPSON EW: Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3'-kinase and phospholipase C-dependent mechanism. Cancer Res. (1999) 59:5475–5478.
  • MAUS MV, REILLY SC, CLEVENGER CV: Prolactin as a chemoattractant for human breast carcinoma. Endocrinology (1999) 140:5447–5450.
  • THEODORESCU D, LADEROUTE KR, GULDING KM: Epidermal growth factor receptor-regulated human bladder cancer motility is in part a phosphatidylinositol 3-kinase-mediated process. Cell Growth Differ (1998) 9:919–928.
  • PUKAC L, HUANGPU J, KARNOVSKY MJ: Platelet-derived growth factor-BB, insulin-like growth factor-I, and phorbol ester activate different signaling pathways for stimulation of vascular smooth muscle cell migration. Exp. Cell Res. (1998) 242:548–560.
  • NAKANISHI K, FUJIMOTO J, UEKI T et al.: Hepatocyte growth factor promotes migration of human hepatocellular carcinoma via phosphatidylinositol 3-kinase. Clin. Exp. Metastasis (1999) 17:507–514.
  • KOTANI K, HARA K, YONEZAWA K, KASUGA M: Phosphoinositide 3-kinase as an upstream regulator of the small GTP-binding protein Rac in the insulin signaling of membrane ruffling. Biochem. Biophys. Res. Commun. (1995) 208:985–990.
  • WENNSTROM S, HAWKINS E COOKE F et al: Activation of phosphoinositide 3-kinase is required for PDGF-stimulated membrane ruffling. Curr. Biol. (1994) 4:385–393.
  • HILL K, WELTI S, YU J et al: Specific requirement for the p85-p1 1 °alpha phosphatidylinositol 3-kinase during epidermal growth factor-stimulated actin nucleation in breast cancer cells. j Biol. Chem. (2000) 275:3741–3744.
  • POSERN G, SAFFRICH R, ANSORGE W, FELLER SM: Rapid lamellipodia formation in nerve growth factor-stimulated PC12 cells is dependent on Rac and PI3K activity. J Cell. Physiol (2000) 183:416–424.
  • SHAW LM, RABINOVITZ I, WANG HH, TOKER A, MERCURIO AM: Activation of phosphoinositide 3-0H kinase by the alpha6beta4 integrin promotes carcinoma invasion. Cell (1997) 91:949–960.
  • GAMBALETTA D, MARCHETTI A, BENEDETTI L, MERCURIO AM, SACCHI A, FALCIONI R: Cooperative signaling between alpha(6)beta(4) integrin and ErbB-2 receptor is required to promote phosphatidylinositol 3-kinase-dependent invasion. j Biol. Chem. (2000) 275:10604–10610.
  • OLSON MF, ASHWORTH A, HALL A: An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through Gl. Science (1995) 269:1270–1272.
  • FRITZ G, JUST I, WOLLENBERG P, AKTORIES K: Differentiation-induced increase in Clostridium botulinum C3 exoenzyme-catalyzed ADP-ribosylation of the small GTP-binding protein Rho. Eur. Biochem. (1994) 223:909–916.
  • HALL A, NOBES CD: Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton. Philos. Trans. R. Soc. Lorid. B. Biol. Sci. (2000) 355:965–970.
  • FRITZ G, JUST I, KAINA B: Rho GTPases are over-expressed in human tumors. Intl Cancer (1999) 81:682–687.
  • KEELY PJ, WESTWICK JK, WHITEHEAD II DER CJ, PARISE LV: Cdc42 and Racl induce integrin-mediated cell motility and invasiveness through PI(3)K. Nature (1997) 390:632–636.
  • ••Highlights interplay between Cdc42, Racland PI3K for regulation of integrin-stimulated cell invasion.
  • BANYARD J, ANAND-APTE B, SYMONS M, ZETTER BR: Motility and invasion are differentially modulated by Rho family GTPases. Oricogerie (2000) 19:580–591.
  • CLARK EA, GOLUB TR, LANDER ES, HYNES RO: Genomic analysis of metastasis reveals an essential role for RhoC. Nature (2000) 406:532–535.
  • ••Demonstrates the value of new, high-throughput array technology to identify novel key players.
  • SUWA H, OHSHIO G, IMAMURA T et al.: Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas. Br Cancer (1998) 77:147–152.
  • ARORA PD, MCCULLOCH CA: Dependence of fibroblast migration on actin severing activity of gelsolin. _J. Biol. Chem. (1996) 271:20516–20523.
  • TURNER T, CHEN P, GOODLY LJ, WELLS A: EGF receptor signaling enhances in vivo invasiveness of DU-145 human prostate carcinoma cells. an. Exp. Metastasis. (1996) 14:409–418.
  • TURNER T, EPPS-FUNG MV, KASSIS J, WELLS A: Molecular inhibition of phospholipase C-gamma signaling abrogates DU-145 prostate tumor cell invasion. Clin Cancer Res. (1997) 3:2275–2282.
  • YI KS, CHUNG JH, LEE YH et al: Inhibition of the EGF-induced activation of phospholipase C-gammal by a single chain antibody fragment. Oricogerie (2001) 20:7954–7964.
  • PARSONS JT, MARTIN KH, SLACK JK, TAYLOR JM, WEED SA: Focal adhesion kinase: a regulator of focal adhesion dynamics and cell movement. Oricogerie (2000) 19:5606–5613.
  • AKASAKA T, VAN LEEUWEN RL, YOSHINAGA IG, MIHM MC JR, BYERS HR: Focal adhesion kinase (p125FAK) expression correlates with motility of human melanoma cell lines. j Invest. Dermatol (1995) 105:104–108.
  • FURUTA Y, ILIC D, KANAZAWA S, TAKEDA N, YAMAMOTO T, AIZAWA S: Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK. Oricogerie (1995) 11:1989–1995.
  • ILIC D, FURUTA Y, KANAZAWA S etal.: Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature (1995) 377:539–544.
  • KORNBERG LJ: Focal adhesion kinase and its potential involvement in tumor invasion and metastasis. Head Neck (1998) 20:745–752.
  • HAUCK CR, SIEG DJ, HSIA DA et al: Inhibition of focal adhesion kinase expression or activity disrupts epidermal growth factor-stimulated signaling promoting the migration of invasive human carcinoma cells. Cancer Res. (2001) 61:7079–7090.
  • ••Demonstrates reduced EGF signalling after FAK inhibition.
  • SLACK JK, ADAMS RB, ROVIN JD, BISSONETTE EA, STOKER CE, PARSONS JT: Alterations in the focal adhesion kinase/Src signal transduction pathway correlate with increased migratory capacity of prostate carcinoma cells. Oncogene (2001) 20:1152–1163.
  • ZHANG X, CHATTOPADHYAY A, JI QS etal.: Focal adhesion kinase promotes phospholipase C-gammal activity. Proc. Natl. Acad. Li. USA (1999) 96:9021–9026.
  • OWEN JD, RUEST PJ, FRY DW, HANKS SK: Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances cell spreading and migration requiring both auto- and activation loop phosphorylation sites and inhibits adhesion-dependent tyrosine phosphorylation of Pyk2. Mol. Cell. Biol. (1999) 19:4806–4818.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.