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Future Oncology Volume 5, 2009 - Issue 7
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Review

Micrometastatic Disease and Metastatic Outgrowth: Clinical Issues and Experimental Approaches

Patricia M McGowana Department Medical Biophysics, Room 415, University of Western Ontario, London, ON, Canada. [email protected]View further author information
,
Jennifer M Kirsteinb Department Medical Biophysics, Room 415, University of Western Ontario, London, ON, Canada. [email protected]View further author information
&
Ann F Chambersc London Regional Cancer Program, 790 Commissioners Road East, London, OntarioN6A 4L6, Canada. [email protected]Correspondence[email protected]
View further author information
Pages 1083-1098 | Published online: 30 Sep 2009

Bibliography

  • Sorlie T , TibshiraniR, ParkerJet al.: Repeated observation of breast tumor subtypes in independent gene expression data sets.Proc. Natl Acad. Sci. USA100, 8418–8423 (2003).
  • Sotiriou C , NeoSY, McShaneLMet al.: Breast cancer classification and prognosis based on gene expression profiles from a population-based study.Proc. Natl Acad. Sci. USA100, 10393–10398 (2003).
  • Finak G , BertosN, PepinFet al.: Stromal gene expression predicts clinical outcome in breast cancer.Nat. Med.14, 518–527 (2008).
  • Paik S , TangG, ShakSet al.: Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.J. Clin. Oncol.24, 3726–3734 (2006).
  • Ma XJ , WangZ, RyanPDet al.: A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen.Cancer Cell5, 607–616 (2004).
  • van de Vijver MJ , HeYD, van’t VeerLJet al.: A gene-expression signature as a predictor of survival in breast cancer.N. Engl. J. Med.347, 1999–2009 (2002).
  • Duffy MJ , CrownJ: A personalized approach to cancer treatment: how biomarkers can help.Clin. Chem.54, 1770–1779 (2008).
  • Chambers AF , GroomAC, MacDonaldIC: Dissemination and growth of cancer cells in metastatic sites.Nat. Rev. Cancer2, 563–572 (2002).
  • Hunter KW , CrawfordNP, AlsarrajJ: Mechanisms of metastasis.Breast Cancer Res.10(Suppl. 1), S2 (2008).
  • Steeg PS : Tumor metastasis: mechanistic insights and clinical challenges.Nat. Med.12, 895–904 (2006).
  • Luzzi KJ , MacDonaldIC, SchmidtEEet al.: Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases.Am. J. Pathol.153, 865–873 (1998).
  • Koop S , MacDonaldIC, LuzziKet al.: Fate of melanoma cells entering the microcirculation: over 80% survive and extravasate.Cancer Res.55, 2520–2523 (1995).
  • Koop S , SchmidtEE, MacDonaldICet al.: Independence of metastatic ability and extravasation: metastatic ras-transformed and control fibroblasts extravasate equally well.Proc. Natl Acad. Sci. USA93, 11080–11084 (1996).
  • Weiss L : Metastatic inefficiency.Adv. Cancer Res.54, 159–211 (1990).
  • Fidler IJ : Biological behavior of malignant melanoma cells correlated to their survival in vivo.Cancer Res.35, 218–224 (1975).
  • Diel IJ , KaufmannM, CostaSDet al.: Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status.J. Natl Cancer Inst.88, 1652–1658 (1996).
  • Braun S , PantelK, MullerPet al.: Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer.N. Engl. J. Med.342, 525–533 (2000).
  • Gebauer G , FehmT, MerkleEet al.: Epithelial cells in bone marrow of breast cancer patients at time of primary surgery: clinical outcome during long-term follow-up.J. Clin. Oncol.19, 3669–3674 (2001).
  • Wikman H , VessellaR, PantelK: Cancer micrometastasis and tumour dormancy.APMIS116, 754–770 (2008).
  • Vessella RL , PantelK, MohlaS: Tumor cell dormancy: an NCI workshop report.Cancer Biol. Ther.6, 1496–1504 (2007).
  • Heyn C , RonaldJA, RamadanSSet al.: In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.Magn. Reson. Med.56, 1001–1010 (2006).
  • Naumov GN , TownsonJL, MacDonaldICet al.: Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases.Breast Cancer Res. Treat.82, 199–206 (2003).
  • Naumov GN , MacDonaldIC, WeinmeisterPMet al.: Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy.Cancer Res.62, 2162–2168 (2002).
  • Meng S , TripathyD, FrenkelEPet al.: Circulating tumor cells in patients with breast cancer dormancy.Clin. Cancer Res.10, 8152–8162 (2004).
  • Balic M , LinH, YoungLet al.: Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype.Clin. Cancer Res.12, 5615–5621 (2006).
  • Camara O , KavallarisA, NoschelHet al.: Seeding of epithelial cells into circulation during surgery for breast cancer: the fate of malignant and benign mobilized cells.World J. Surg. Oncol.4, 67 (2006).
  • Suzuki M , MoseES, MontelV, TarinD: Dormant cancer cells retrieved from metastasis-free organs regain tumorigenic and metastatic potency.Am. J. Pathol.169, 673–681 (2006).
  • Naumov GN , BenderE, ZurakowskiDet al.: A model of human tumor dormancy: an angiogenic switch from the nonangiogenic phenotype.J. Natl Cancer Inst.98, 316–325 (2006).
  • Holmgren L , O’ReillyMS, FolkmanJ: Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression.Nat. Med.1, 149–153 (1995).
  • Wiedswang G , BorgenE, KaresenRet al.: Isolated tumor cells in bone marrow three years after diagnosis in disease-free breast cancer patients predict unfavorable clinical outcome.Clin. Cancer Res.10, 5342–5348 (2004).
  • Braun S , KentenichC, JanniWet al.: Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients.J. Clin. Oncol.18, 80–86 (2000).
  • Becker S , Becker-PergolaG, WallwienerD, SolomayerEF, FehmT: Detection of cytokeratin-positive cells in the bone marrow of breast cancer patients undergoing adjuvant therapy.Breast Cancer Res. Treat.97, 91–96 (2006).
  • Goldhirsch A , WoodWC, GelberRDet al.: Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007.Ann. Oncol.18, 1133–1144 (2007).
  • Harris L , FritscheH, MennelRet al.: American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer.J. Clin. Oncol.25, 5287–5312 (2007).
  • Goss P , AllanAL, RodenhiserDI, FosterPJ, ChambersAF: New clinical and experimental approaches for studying tumor dormancy: does tumor dormancy offer a therapeutic target?APMIS116, 552–568 (2008).
  • Mansi JL , GogasH, BlissJMet al.: Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study.Lancet354, 197–202 (1999).
  • Mansi JL , EastonD, BergerUet al.: Bone marrow micrometastases in primary breast cancer: prognostic significance after 6 years’ follow-up.Eur. J. Cancer27, 1552–1555 (1991).
  • Braun S , VoglFD, NaumeBet al.: A pooled analysis of bone marrow micrometastasis in breast cancer.N. Engl. J. Med.353, 793–802 (2005).
  • Kollermann J , WeikertS, SchostakMet al.: Prognostic significance of disseminated tumor cells in the bone marrow of prostate cancer patients treated with neoadjuvant hormone treatment.J. Clin. Oncol.26, 4928–4933 (2008).
  • Goodman OB Jr , FinkLM, SymanowskiJTet al.: Circulating tumor cells in patients with castration-resistant prostate cancer baseline values and correlation with prognostic factors.Cancer Epidemiol. Biomarkers Prev.18, 1904–1913 (2009).
  • Pantel K , Alix-PanabieresC, RiethdorfS: Cancer micrometastases.Nat. Rev. Clin. Oncol.6(6), 339–351 (2009).
  • Theodoropoulos PA , PolioudakiH, SanidasEet al. Detection of circulating tumor cells with breast cancer stem cell-like phenotype in blood samples of patients with breast cancer. Presented at: AACR. San Diego, CA, USA, 12–16 April 2008.
  • Croker AK , TownsonJL, AllanAL, ChambersAF: Tumor dormancy, metastasis and cancer stem cells. In: Stem Cells and Cancer (Cancer Drug Discovery and Development). BagleyR, TeicherB (Eds). Humana Press, Springer, NY, USA141–153 (2009).
  • Townson JL , ChambersAF: Dormancy of solitary metastatic cells.Cell Cycle5, 1744–1750 (2006).
  • Brackstone M , TownsonJL, ChambersAF: Tumour dormancy in breast cancer: an update.Breast Cancer Res.9, 208 (2007).
  • Naumov GN , AkslenLA, FolkmanJ: Role of angiogenesis in human tumor dormancy: animal models of the angiogenic switch.Cell Cycle5, 1779–1787 (2006).
  • Naumov GN , MacDonaldIC, ChambersAF, GroomAC: Solitary cancer cells as a possible source of tumour dormancy?Semin. Cancer Biol.11, 271–276 (2001).
  • Cameron MD , SchmidtEE, KerkvlietNet al.: Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency.Cancer Res.60, 2541–2546 (2000).
  • Heyn C , RonaldJA, MackenzieLTet al.: In vivo magnetic resonance imaging of single cells in mouse brain with optical validation.Magn. Reson. Med.55, 23–29 (2006).
  • Strijkers GJ , MulderWJ, van TilborgGA, NicolayK: MRI contrast agents: current status and future perspectives.Anticancer Agents Med. Chem.7, 291–305 (2007).
  • Weissleder R , ChengHC, BogdanovaA, BogdanovAJr: Magnetically labeled cells can be detected by MR imaging.J. Magn. Reson. Imaging7, 258–263 (1997).
  • Indraccolo S , FavaroE, AmadoriA: Dormant tumors awaken by a short-term angiogenic burst: the spike hypothesis.Cell Cycle5, 1751–1755 (2006).
  • Indraccolo S , StievanoL, MinuzzoSet al.: Interruption of tumor dormancy by a transient angiogenic burst within the tumor microenvironment.Proc. Natl Acad. Sci. USA103, 4216–4221 (2006).
  • Logan PT , FernandesBF, Di CesareSet al.: Single-cell tumor dormancy model of uveal melanoma.Clin. Exp. Metastasis25, 509–516 (2008).
  • Bao L , PigottR, MatsumuraY, BabanD, TarinD: Correlation of VLA-4 integrin expression with metastatic potential in various human tumour cell lines.Differentiation52, 239–246 (1993).
  • Urquidi V , SloanD, KawaiKet al.: Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis.Clin. Cancer Res.8, 61–74 (2002).
  • Goodison S , KawaiK, HiharaJet al.: Prolonged dormancy and site-specific growth potential of cancer cells spontaneously disseminated from nonmetastatic breast tumors as revealed by labeling with green fluorescent protein.Clin. Cancer Res.9, 3808–3814 (2003).
  • Demicheli R , AbbattistaA, MiceliR, ValagussaP, BonadonnaG: Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: further support about the concept of tumor dormancy.Breast Cancer Res. Treat.41, 177–185 (1996).
  • Karrison TG , FergusonDJ, MeierP: Dormancy of mammary carcinoma after mastectomy.J. Natl Cancer Inst.91, 80–85 (1999).
  • Demicheli R , RetskyMW, SwartzendruberDE, BonadonnaG: Proposal for a new model of breast cancer metastatic development.Ann. Oncol.8, 1075–1080 (1997).
  • Retsky MW , DemicheliR, SwartzendruberDEet al.: Computer simulation of a breast cancer metastasis model.Breast Cancer Res. Treat.45, 193–202 (1997).
  • Demicheli R , RetskyMW, HrusheskyWJ, BaumM: Tumor dormancy and surgery-driven interruption of dormancy in breast cancer: learning from failures.Nat. Clin. Pract. Oncol.4, 699–710 (2007).
  • O’Reilly MS , HolmgrenL, ChenC, FolkmanJ: Angiostatin induces and sustains dormancy of human primary tumors in mice.Nat. Med.2, 689–692 (1996).
  • Guba M , CernaianuG, KoehlGet al.: A primary tumor promotes dormancy of solitary tumor cells before inhibiting angiogenesis.Cancer Res.61, 5575–5579 (2001).
  • Chambers AF , GossPE: Putative growth characteristics of micrometastatic breast cancer.Breast Cancer Res.10, 114 (2008).
  • Demicheli R , BiganzoliE, BoracchiP, GrecoM, RetskyMW: Recurrence dynamics does not depend on the recurrence site.Breast Cancer Res.10, R83 (2008).
  • O’Reilly MS , BoehmT, ShingYet al.: Endostatin: an endogenous inhibitor of angiogenesis and tumor growth.Cell88, 277–285 (1997).
  • Peeters CF , de WaalRM, WobbesT, RuersTJ: Metastatic dormancy imposed by the primary tumor: does it exist in humans?Ann. Surg. Oncol.15, 3308–3315 (2008).
  • Goss PE , IngleJN, MartinoSet al.: A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer.N. Engl. J. Med.349, 1793–1802 (2003).
  • Goss PE : Letrozole in the extended adjuvant setting: MA.17.Breast Cancer Res. Treat.105(Suppl. 1), 45–53 (2007).
  • Moy B , GossPE: TEACH: Tykerb evaluation after chemotherapy.Clin. Breast Cancer7, 489–492 (2007).
  • Pittet MJ : Behavior of immune players in the tumor microenvironment.Curr. Opin. Oncol.21, 53–59 (2009).
  • de la Cruz-Merino L , Grande-PulidoE, Albero-TamaritA, Codes-Manuel de VillenaME: Cancer and immune response: old and new evidence for future challenges.Oncologist13, 1246–1254 (2008).
  • Davis TA , MaloneyDG, CzerwinskiDK, LilesTM, LevyR: Anti-idiotype antibodies can induce long-term complete remissions in non-Hodgkin’s lymphoma without eradicating the malignant clone.Blood92, 1184–1190 (1998).
  • Montagna D , MaccarioR, LocatelliFet al.: Emergence of antitumor cytolytic T cells is associated with maintenance of hematologic remission in children with acute myeloid leukemia.Blood108, 3843–3850 (2006).
  • Pantel K , CoteRJ, FodstadO: Detection and clinical importance of micrometastatic disease.J. Natl Cancer Inst.91, 1113–1124 (1999).
  • Schirrmacher V : T-cell immunity in the induction and maintenance of a tumour dormant state.Semin. Cancer Biol.11, 285–295 (2001).
  • Weinhold KJ , GoldsteinLT, WheelockEF: The tumor dormant state. Quantitation of L5178Y cells and host immune responses during the establishment and course of dormancy in syngeneic DBA/2 mice.J. Exp. Med.149, 732–744 (1979).
  • Kauffman HM , CherikhWS, ChengY: Posttransplantation malignancies: a problem, a challenge, and an opportunity.Liver Transpl.8, 488–490 (2002).
  • Kauffman HM : Malignancies in organ transplant recipients.J. Surg. Oncol.94, 431–433 (2006).
  • Koebel CM , VermiW, SwannJBet al.: Adaptive immunity maintains occult cancer in an equilibrium state.Nature450, 903–907 (2007).
  • Saudemont A , QuesnelB: In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis.Blood104, 2124–2133 (2004).
  • Indraccolo S , MinuzzoS, MasieroMet al.: Cross-talk between tumor and endothelial cells involving the Notch3-Dll4 interaction marks escape from tumor dormancy.Cancer Res.69, 1314–1323 (2009).
  • Almog N , MaL, RaychowdhuryRet al.: Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype.Cancer Res.69, 836–844 (2009).
  • Janes PW , AdikariS, LackmannM: Eph/ephrin signalling and function in oncogenesis: lessons from embryonic development.Curr. Cancer Drug Targets8, 473–479 (2008).
  • Mbeunkui F , JohannDJJr: Cancer and the tumor microenvironment: a review of an essential relationship.Cancer Chemother. Pharmacol.63, 571–582 (2009).
  • Barkan D , KleinmanH, SimmonsJLet al.: Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton.Cancer Res.68, 6241–6250 (2008).
  • Erler JT , WeaverVM: Three-dimensional context regulation of metastasis.Clin. Exp. Metastasis26, 35–49 (2009).
  • Lunt SJ , ChaudaryN, HillRP: The tumor microenvironment and metastatic disease.Clin. Exp. Metastasis26, 19–34 (2009).
  • Chambers AF : Influence of diet on metastasis and tumor dormancy.Clin. Exp. Metastasis26, 61–66 (2009).
  • Schmidt CM , SettleSL, KeeneJLet al.: Characterization of spontaneous metastasis in an aggressive breast carcinoma model using flow cytometry.Clin. Exp. Metastasis17, 537–544 (1999).
  • Vantyghem SA , WilsonSM, PostenkaCOet al.: Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model.Cancer Res.65, 3396–3403 (2005).
  • Hattar R , MallerO, McDanielSet al.: Tamoxifen induces pleiotrophic changes in mammary stroma resulting in extracellular matrix that suppresses transformed phenotypes.Breast Cancer Res.11, R5 (2009).
  • Bambang IF , LuD, LiHet al.: Cytokeratin 19 regulates endoplasmic reticulum stress and inhibits ERp29 expression via p38 MAPK/XBP-1 signaling in breast cancer cells.Exp. Cell Res.315(11), 1964–1974 (2009).
  • Ranganathan AC , ZhangL, AdamAP, Aguirre-GhisoJA: Functional coupling of p38-induced up-regulation of BiP and activation of RNA-dependent protein kinase-like endoplasmic reticulum kinase to drug resistance of dormant carcinoma cells.Cancer Res.66, 1702–1711 (2006).
  • Ranganathan AC , AdamAP, Aguirre-GhisoJA: Opposing roles of mitogenic and stress signaling pathways in the induction of cancer dormancy.Cell Cycle5, 1799–1807 (2006).
  • Ranganathan AC , AdamAP, ZhangL, Aguirre-GhisoJA: Tumor cell dormancy induced by p38SAPK and ER-stress signaling: an adaptive advantage for metastatic cells?Cancer Biol. Ther.5, 729–735 (2006).
  • Pruitt K , PruittWM, BilterGK, WestwickJK, DerCJ: Raf-independent deregulation of p38 and JNK mitogen-activated protein kinases are critical for Ras transformation.J. Biol. Chem.277, 31808–31817 (2002).
  • Aguirre-Ghiso JA , EstradaY, LiuD, OssowskiL: ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK).Cancer Res.63, 1684–1695 (2003).
  • Schewe DM , Aguirre-GhisoJA: ATF6α–Rheb–mTOR signaling promotes survival of dormant tumor cells in vivo.Proc. Natl Acad. Sci. USA105, 10519–10524 (2008).
  • Gozuacik D , KimchiA: Autophagy as a cell death and tumor suppressor mechanism.Oncogene23, 2891–2906 (2004).
  • Marx J : Autophagy: is it cancer’s friend or foe?Science312, 1160–1161 (2006).
  • Botti J , Djavaheri-MergnyM, PilatteY, CodognoP: Autophagy signaling and the cogwheels of cancer.Autophagy2, 67–73 (2006).
  • Lu Z , LuoRZ, LuYet al.: The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells.J. Clin. Invest.118, 3917–3929 (2008).
  • Dvorak F , RicklesF: Malignancy and hemostasis. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice. ColemanR, MarderV, ClowesA, GeorgeJ, GoldhaberS (Eds). Lippincott Company Wiliams & Wilkins, PA, USA851–873 (2006).
  • Palumbo JS , KombrinckKW, DrewAFet al.: Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells.Blood96, 3302–3309 (2000).
  • Staton CA , BrownNJ, LewisCE: The role of fibrinogen and related fragments in tumour angiogenesis and metastasis.Expert Opin. Biol. Ther.3, 1105–1120 (2003).
  • Im JH , FuW, WangHet al.: Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation.Cancer Res.64, 8613–8619 (2004).
  • Esumi N , FanD, FidlerIJ: Inhibition of murine melanoma experimental metastasis by recombinant desulfatohirudin, a highly specific thrombin inhibitor.Cancer Res.51, 4549–4556 (1991).
  • Palumbo JS , TalmageKE, MassariJVet al.: Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells.Blood105, 178–185 (2005).
  • Biggerstaff JP , WeidowB, VidoshJet al.: Soluble fibrin inhibits monocyte adherence and cytotoxicity against tumor cells: implications for cancer metastasis.Thromb. J.4, 12 (2006).
  • Camerer E , QaziAA, DuongDNet al.: Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis.Blood104, 397–401 (2004).
  • Palumbo JS , TalmageKE, MassariJVet al.: Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms.Blood110, 133–141 (2007).
  • Nieswandt B , HafnerM, EchtenacherB, MannelDN: Lysis of tumor cells by natural killer cells in mice is impeded by platelets.Cancer Res.59, 1295–1300 (1999).
  • Kirstein JM , GrahamKC, MackenzieLTet al.: Effect of anti-fibrinolytic therapy on experimental melanoma metastasis.Clin. Exp. Metastasis26, 121–131 (2009).
  • Niers TM , KlerkCP, DiNisioMet al.: Mechanisms of heparin induced anti-cancer activity in experimental cancer models.Crit. Rev. Oncol. Hematol.61, 195–207 (2007).
  • Lee AY , RicklesFR, JulianJAet al.: Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism.J. Clin. Oncol.23, 2123–2129 (2005).
  • Schulman S , LindmarkerP: Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. Duration of anticoagulation trial.N. Engl. J. Med.342, 1953–1958 (2000).
  • Nierodzik ML , KarpatkinS: Thrombin induces tumor growth, metastasis, and angiogenesis: Evidence for a thrombin-regulated dormant tumor phenotype.Cancer Cell10, 355–362 (2006).
  • Rak J , MilsomC, YuJ: Vascular determinants of cancer stem cell dormancy – do age and coagulation system play a role?APMIS116, 660–676 (2008).
  • Brill A , DashevskyO, RivoJ, GozalY, VaronD: Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization.Cardiovasc. Res.67, 30–38 (2005).
  • Brill A , ElinavH, VaronD: Differential role of platelet granular mediators in angiogenesis.Cardiovasc. Res.63, 226–235 (2004).
  • Croker AK , AllanAL: Cancer stem cells: implications for the progression and treatment of metastatic disease.J. Cell. Mol. Med.12, 374–390 (2008).
  • Allan AL , VantyghemSA, TuckAB, ChambersAF: Tumor dormancy and cancer stem cells: implications for the biology and treatment of breast cancer metastasis.Breast Dis.26, 87–98 (2006).
  • Shackleton M , VaillantF, SimpsonKJet al.: Generation of a functional mammary gland from a single stem cell.Nature439, 84–88 (2006).
  • Stingl J , RaoufA, EmermanJT, EavesCJ: Epithelial progenitors in the normal human mammary gland.J. Mammary Gland Biol. Neoplasia10, 49–59 (2005).
  • Tanentzapf G , DevenportD, GodtD, BrownNH: Integrin-dependent anchoring of a stem-cell niche.Nat. Cell Biol.9, 1413–1418 (2007).
  • Benitah SA , FryeM, GlogauerM, WattFM: Stem cell depletion through epidermal deletion of Rac1.Science309, 933–935 (2005).
  • Campos LS , DeckerL, TaylorV, SkarnesW: Notch, epidermal growth factor receptor, and β1-integrin pathways are coordinated in neural stem cells.J. Biol. Chem.281, 5300–5309 (2006).
  • Campos LS , LeoneDP, RelvasJBet al.: β1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance.Development131, 3433–3444 (2004).
  • Shachaf CM , KopelmanAM, ArvanitisCet al.: MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer.Nature431, 1112–1117 (2004).
  • Yefenof E : Murine models of thymic lymphomas: premalignant scenarios amenable to prophylactic therapy.Adv. Immunol.73, 511–539 (1999).
  • Uhr JW , MarchesR: Dormancy in a model of murine B cell lymphoma.Semin. Cancer Biol.11, 277–283 (2001).
  • Uhr JW , TuckerT, MayRD, SiuH, VitettaES: Cancer dormancy: studies of the murine BCL1 lymphoma.Cancer Res.51, 5045S–5053S (1991).
  • Farrar JD , KatzKH, WindsorJet al.: Cancer dormancy. VII. A regulatory role for CD8+ T cells and IFN-γ in establishing and maintaining the tumor-dormant state.J. Immunol.162, 2842–2849 (1999).
  • Vereecque R , BuffenoirG, GonzalezRet al.: A new murine aggressive leukemic model.Leuk. Res.23, 415–416 (1999).
  • Morris VL , MacDonaldIC, KoopSet al.: Early interactions of cancer cells with the microvasculature in mouse liver and muscle during hematogenous metastasis: videomicroscopic analysis.Clin. Exp. Metastasis11, 377–390 (1993).
  • Aguirre-Ghiso JA , OssowskiL, RosenbaumSK: Green fluorescent protein tagging of extracellular signal-regulated kinase and p38 pathways reveals novel dynamics of pathway activation during primary and metastatic growth.Cancer Res.64, 7336–7345 (2004).
  • Aguirre-Ghiso JA , LiuD, MignattiA, KovalskiK, OssowskiL: Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo.Mol. Biol. Cell12, 863–879 (2001).
  • Muller-Hermelink N , BraumullerH, PichlerBet al.: TNFR1 signaling and IFN-γ signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis.Cancer Cell13, 507–518 (2008).
  • Saudemont A , JouyN, HetuinD, QuesnelB: NK cells that are activated by CXCL10 can kill dormant tumor cells that resist CTL-mediated lysis and can express B7-H1 that stimulates T cells.Blood105, 2428–2435 (2005).
  • Chaurasia P , Aguirre-GhisoJA, LiangODet al.: A region in urokinase plasminogen receptor domain III controlling a functional association with α5β1 integrin and tumor growth.J. Biol. Chem.281, 14852–14863 (2006).
  • Aguirre Ghiso JA , KovalskiK, OssowskiL: Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling.J. Cell. Biol.147, 89–104 (1999).
  • Lim ST , ChenXL, LimYet al.: Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation.Mol. Cell29, 9–22 (2008).
  • Laufs S , SchumacherJ, AllgayerH: Urokinase-receptor (u-PAR): an essential player in multiple games of cancer: a review on its role in tumor progression, invasion, metastasis, proliferation/dormancy, clinical outcome and minimal residual disease.Cell Cycle5, 1760–1771 (2006).
  • Aguirre-Ghiso JA : Models, mechanisms and clinical evidence for cancer dormancy.Nat. Rev. Cancer7, 834–846 (2007).

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