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Research Paper

Lipopolysaccharide (LPS) stimulation of Pancreatic Ductal Adenocarcinoma (PDAC) and macrophages activates the NLRP3 inflammasome that influences the levels of pro-inflammatory cytokines in a co-culture model

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Article: 2284857 | Received 05 May 2022, Accepted 14 Nov 2023, Published online: 29 Nov 2023

References

  • McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG, McCain RS. Pancreatic cancer: a review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 2018 Nov 21;24(43):4846–12. doi:10.3748/wjg.v24.i43.4846.
  • Laheru D. 2020. Pancreatic cancer. Goldman-Cecil Med 26th Ed: Chapter. 185:1305–1308.e1302.
  • Wadsworth C. 2021. Biliary tract and pancreatic disease. Kumar And Clark’s Clin Med. 35:1313–1337.
  • Guo JY, Chen H-Y, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G, Kamphorst JJ, Chen G, Lemons JMS, Karantza V, et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 2011;25(5):460–470. doi:10.1101/gad.2016311.
  • Ling J, Kang Y, Zhao R, Xia Q, Lee D-F, Chang Z, Li J, Peng B, Fleming J, Wang H, et al. KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;21(1):105–120. doi:10.1016/j.ccr.2011.12.006.
  • Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, Bause A, Li Y, Stommel JM, Dell’Antonio G, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 2011;25(7):717–729. doi:10.1101/gad.2016111.
  • Kopp JL, von Figura G, Mayes E, Liu F-F, Dubois C, Morris J, Pan F, Akiyama H, Wright CE, Jensen K, et al. Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;22(6):737–750. doi:10.1016/j.ccr.2012.10.025.
  • Chen C, Edelstein LC, Gélinas C. The Rel/NF-κB family directly activates expression of the apoptosis inhibitor Bcl-x L. Mol Cell Biol. 2000;20(8):2687–2695. doi:10.1128/MCB.20.8.2687-2695.2000.
  • Erkan M, Hausmann S, Michalski CW, Fingerle AA, Dobritz M, Kleeff J, Friess H. The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol. 2012;9(8):454–467. doi:10.1038/nrgastro.2012.115.
  • Liptay S, Weber CK, Ludwig L, Wagner M, Adler G, Schmid RM. Mitogenic and antiapoptotic role of constitutive NF-κB/Rel activity in pancreatic cancer. Int J Cancer. 2003;105(6):735–746. doi:10.1002/ijc.11081.
  • Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Sig Transduct Target Ther. 2017;2(1):17023. doi:10.1038/sigtrans.2017.23.
  • Romashkova JA, Makarov SS. NF-κB is a target of AKT in anti-apoptotic PDGF signalling. Nature. 1999;401(6748):86–90. doi:10.1038/43474.
  • Guerra C, Collado M, Navas C, Schuhmacher A, Hernández-Porras I, Cañamero M, Rodriguez-Justo M, Serrano M, Barbacid M. Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell. 2011;19(6):728–739. doi:10.1016/j.ccr.2011.05.011.
  • Hu H, Jiao F, Han T, Wang L-W. Functional significance of macrophages in pancreatic cancer biology. Tumor Biol. 2015;36(12):9119–9126. doi:10.1007/s13277-015-4127-2.
  • Galdiero MR, Biswas SK, Mantovani A. Polarized activation of macrophages. In: Biswas SK, and Mantovani A, editors Macrophages: biology and role in the pathology of diseases. New York, NY: Springer New York; 2014. pp. 37–57.
  • Sica A, Straus L, Allavena P. Tumor-associated macrophages. In: Biswas SK, and Mantovani A, editors Macrophages: biology and role in the pathology of diseases. New York, NY: Springer New York; 2014. pp. 425–443.
  • Wang X, Luo G, Zhang K, Cao J, Huang C, Jiang T, Liu B, Su L, Qiu Z. Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kγ to Promote Pancreatic Cancer Metastasis. Cancer Res. 2018;78(16):4586–4598. doi:10.1158/0008-5472.CAN-17-3841.
  • Xiong C, Zhu Y, Xue M, Jiang Y, Zhong Y, Jiang L, Shi M, Chen H. Tumor-associated macrophages promote pancreatic ductal adenocarcinoma progression by inducing epithelial-to-mesenchymal transition. Aging. 2021;13(3):3386–3404. doi:10.18632/aging.202264.
  • Sharma BR, Kanneganti T-D. NLRP3 inflammasome in cancer and metabolic diseases. Nat Immunol. 2021;22(5):550–559. doi:10.1038/s41590-021-00886-5.
  • Daley D, Mani VR, Mohan N, Akkad N, Pandian GSDB, Savadkar S, Lee KB, Torres-Hernandez A, Aykut B, Diskin B, et al. NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma. J Exp Med. 2017;214(6):1711–1724. doi:10.1084/jem.20161707.
  • Groslambert M, Py B. Spotlight on the NLRP3 inflammasome pathway. JIR. 2018;11:359–374. doi:10.2147/JIR.S141220.
  • Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci. 2019;20(13):3328. doi:10.3390/ijms20133328.
  • Swanson KV, Deng M, Ting JPY. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19(8):477–489. doi:10.1038/s41577-019-0165-0.
  • Baker KJ, Houston A, Brint E. IL-1 family members in cancer; two sides to every story. Front Immunol. 2019;10:1197–1197. doi:10.3389/fimmu.2019.01197.
  • Sun Y, Guo Y. Expression of caspase-1 in breast cancer tissues and its effects on cell proliferation, apoptosis and invasion. Oncol Lett. 2018;15(5):6431–6435. doi:10.3892/ol.2018.8176.
  • Thi HTH, Hong S. Inflammasome as a therapeutic target for cancer prevention and treatment. J Cancer Prev. 2017;22(2):62–73. doi:10.15430/JCP.2017.22.2.62.
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–264. doi:10.1038/nrc3239.
  • Greten FR, Weber CK, Greten TF, Schneider G, Wagner M, Adler G, Schmid RM. Stat3 and NF-κB activation prevents apoptosis in pancreatic carcinogenesis. Gastroenterology. 2002;123(6):2052–2063. doi:10.1053/gast.2002.37075.
  • Zhang Z, Rigas B. NF-κB, inflammation and pancreatic carcinogenesis: NF-κB as a chemoprevention target (Review). Int J Oncol. 2006;29(1):185–192. doi:10.3892/ijo.29.1.185.
  • Gaiser RA, Halimi A, Alkharaan H, Lu L, Davanian H, Healy K, Hugerth LW, Ateeb Z, Valente R, Fernández Moro C, et al. Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer. Gut. 2019;68(12):2186–2194. doi:10.1136/gutjnl-2018-317458.
  • Das S, Shapiro B, Vucic EA, Vogt S, Bar-Sagi D. Tumor cell–derived IL1β promotes desmoplasia and immune Suppression in pancreatic cancer. Cancer Res. 2020;80(5):1088–1101. doi:10.1158/0008-5472.CAN-19-2080.
  • Flint TR, Janowitz T, Connell C, Roberts E, Denton A, Coll A, Jodrell D, Fearon D. Tumor-induced IL-6 reprograms Host metabolism to suppress anti-tumor immunity. Cell Metab. 2016;24(5):672–684. doi:10.1016/j.cmet.2016.10.010.
  • Wang X, Lin Y. Tumor necrosis factor and cancer, buddies or foes? Acta Pharmacol Sin. 2008;29(11):1275–1288. doi:10.1111/j.1745-7254.2008.00889.x.
  • Zelová H, Hošek J. TNF-α signalling and inflammation: interactions between old acquaintances. Inflamm Res. 2013;62(7):641–651. doi:10.1007/s00011-013-0633-0.
  • Balkwill F. TNF-α in promotion and progression of cancer. Cancer Metastasis Rev. 2006;25(3):409–416. doi:10.1007/s10555-006-9005-3.
  • Sethi G, Shanmugam M, Ramachandran L, Kumar A, Tergaonkar V. Multifaceted link between cancer and inflammation. Biosci Rep. 2011;32(1):1–15. doi:10.1042/BSR20100136.
  • McGeough MD, Wree A, Inzaugarat ME, Haimovich A, Johnson CD, Peña CA, Goldbach-Mansky R, Broderick L, Feldstein AE, Hoffman HM. TNF regulates transcription of NLRP3 inflammasome components and inflammatory molecules in cryopyrinopathies. J Clin Invest. 2017;127(12):4488–4497. doi:10.1172/JCI90699.
  • Neta R, Sayers TJ, Oppenheim JJ. 1992. Relationship of TNF to interleukins. Immunol Ser. 56:499–566.
  • Wu D, Chen Y, Sun Y, Gao Q, Li H, Yang Z, Wang Y, Jiang X, Yu B. Target of MCC950 in inhibition of NLRP3 inflammasome activation: a literature review. Inflammation. 2020;43(1):17–23. doi:10.1007/s10753-019-01098-8.
  • Chen S-P, Zhou Y-Q, Wang X-M, Sun J, Cao F, HaiSam S, Ye D-W, Tian Y-K. Pharmacological inhibition of the NLRP3 inflammasome as a potential target for cancer-induced bone pain. Pharmacol Res. 2019;147:104339. doi:10.1016/j.phrs.2019.104339.
  • Huang C-F, Chen L, Li Y-C, Wu L, Yu G-T, Zhang W-F, Sun Z-J. NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma. J Exp Clin Cancer Res. 2017;36(1):116. doi:10.1186/s13046-017-0589-y.
  • Shi J, Xue J. Inflammation and development of pancreatic ductal adenocarcinoma. Chin Clin Oncol. 2019;8(2):19–19. doi:10.21037/cco.2019.04.02.
  • Kong X, Sun T, Kong F, Du Y, Li Z. Chronic pancreatitis and pancreatic cancer. Gastrointest Tumors. 2014;1(3):123–134. doi:10.1159/000365306.
  • Hausmann S, Kong, B., Michalski, C., Erkan, M. and Friess, H. The role of inflammation in pancreatic cancer. In: Aggarwal BB, Sung B Gupta SC, editors Inflammation and cancer. Basel: Springer Basel; 2014. pp. 129–151.
  • Kolodecik T, Shugrue C, Ashat M, Thrower EC. Risk factors for pancreatic cancer: underlying mechanisms and potential targets. Front Physiol. 2014;4:415–415. doi:10.3389/fphys.2013.00415.
  • Yaw ACK, Chan EWL, Yap JKY, Mai CW. The effects of NLRP3 inflammasome inhibition by MCC950 on LPS-induced pancreatic adenocarcinoma inflammation. J Cancer Res Clin Oncol. 2020;146(9):2219–2229. doi:10.1007/s00432-020-03274-y.
  • Chantôme A, Pance A, Gauthier N, Vandroux D, Chenu J, Solary E, Jeannin J-F, Reveneau S. Casein Kinase II-mediated phosphorylation of NF-κB p65 Subunit enhances Inducible Nitric-oxide synthase gene transcription in Vivo*. J Biol Chem. 2004;279(23):23953–23960. doi:10.1074/jbc.M313731200.
  • Cornut M, Bourdonnay E, Henry T. Transcriptional regulation of inflammasomes. Int J Mol Sci. 2020;21(21):8087. doi:10.3390/ijms21218087.
  • Engström A, Erlandsson A, Delbro D, Wijkander J. Conditioned media from macrophages of M1, but not M2 phenotype, inhibit the proliferation of the colon cancer cell lines HT-29 and CACO-2. Int J Oncol. 2014;44(2):385–392. doi:10.3892/ijo.2013.2203.
  • Tao M, Liu L, Shen M, Zhi Q, Gong F-R, Zhou BP, Wu Y, Liu H, Chen K, Shen B, et al. Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac. Cell Cycle (Georgetown, Tex). 2016;15(3):381–393. doi:10.1080/15384101.2015.1127468.
  • Corcoran RB, Contino G, Deshpande V, Tzatsos A, Conrad C, Benes CH, Levy DE, Settleman J, Engelman JA, Bardeesy N. STAT3 plays a Critical role in KRAS-induced pancreatic Tumorigenesis. Cancer Res. 2011;71(14):5020–5029. doi:10.1158/0008-5472.CAN-11-0908.
  • Mollinedo F, Gajate C. Novel therapeutic approaches for pancreatic cancer by combined targeting of RAF→MEK→ERK signaling and autophagy survival response. Ann Transl Med. 2019;7(Suppl S3):S153–S153. doi:10.21037/atm.2019.06.40.
  • Storz P. Targeting protein kinase C subtypes in pancreatic cancer. Expert Rev Anticancer Ther. 2015;15(4):433–438. doi:10.1586/14737140.2015.1003810.
  • Takahashi R, Hirata Y, Sakitani K, Nakata W, Kinoshita H, Hayakawa Y, Nakagawa H, Sakamoto K, Hikiba Y, Ijichi H, et al. Therapeutic effect of c-Jun N-terminal kinase inhibition on pancreatic cancer. Cancer Sci. 2013;104(3):337–344. doi:10.1111/cas.12080.
  • Coll RC, Hill JR, Day CJ, Zamoshnikova A, Boucher D, Massey NL, Chitty JL, Fraser JA, Jennings MP, Robertson AAB, et al. MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nat Chem Biol. 2019;15(6):556–559. doi:10.1038/s41589-019-0277-7.
  • He Y, Hara H, Núñez G. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci. 2016;41(12):1012–1021. doi:10.1016/j.tibs.2016.09.002.
  • Song H, Liu B, Huai W, Yu Z, Wang W, Zhao J, Han L, Jiang G, Zhang L, Gao C, et al. The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by promoting proteasomal degradation of NLRP3. Nat Commun. 2016;7(1):13727. doi:10.1038/ncomms13727.
  • Zhu L, Meng Q, Liang S, Ma Y, Li R, Li G, Zeng H. The transcription factor GFI1 negatively regulates NLRP3 inflammasome activation in macrophages. FEBS Lett. 2014;588(23):4513–4519. doi:10.1016/j.febslet.2014.10.025.
  • Wang B, Wei H, Prabhu L, Zhao W, Martin M, Hartley A-V, Lu T. Role of Novel Serine 316 phosphorylation of the p65 subunit of NF-κB in differential gene regulation. J Biol Chem. 2015;290(33):20336–20347. doi:10.1074/jbc.M115.639849.