Fibroblasts in pancreatic cancer: molecular and clinical perspectives

Trends in Molecular Medicine - Tập 29 - Trang 439-453 - 2023
Rita Rebelo1,2,3, Cristina P.R. Xavier1,2, Elisa Giovannetti4,5, M. Helena Vasconcelos1,2,3
1Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal
2Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, 4200-135 Porto, Portugal
3Department of Biological Sciences, Faculty of Pharmacy of the University of Porto (FFUP), Porto, Portugal
4Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
5Fondazione Pisana Per La Scienza, Pisa, Italy

Tài liệu tham khảo

Ho, 2020, The tumour microenvironment in pancreatic cancer – clinical challenges and opportunities, Nat. Rev. Clin. Oncol., 17, 527, 10.1038/s41571-020-0363-5 Kalluri, 2016, The biology and function of fibroblasts in cancer, Nat. Rev. Cancer, 16, 582, 10.1038/nrc.2016.73 Bachem, 1998, Identification, culture, and characterization of pancreatic stellate cells in rats and humans, Gastroenterology, 115, 421, 10.1016/S0016-5085(98)70209-4 Apte, 1998, Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture, Gut, 43, 128, 10.1136/gut.43.1.128 Erkan, 2012, StellaTUM: current consensus and discussion on pancreatic stellate cell research, Gut, 61, 172, 10.1136/gutjnl-2011-301220 Biffi, 2021, Diversity and biology of cancer-associated fibroblasts, Physiol. Rev., 101, 147, 10.1152/physrev.00048.2019 Tian, 2016, Activation of pancreatic stellate cells involves an EMT-like process, Int. J. Oncol., 48, 783, 10.3892/ijo.2015.3282 Ozdemir, 2014, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Cancer Cell, 25, 719, 10.1016/j.ccr.2014.04.005 Ramanathan, 2019, Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313, J. Clin. Oncol., 37, 1062, 10.1200/JCO.18.01295 Djurec, 2018, Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors, Proc. Natl. Acad. Sci. U. S. A., 115, E1147, 10.1073/pnas.1717802115 Elyada, 2019, Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts, Cancer Discov., 9, 1102, 10.1158/2159-8290.CD-19-0094 Ohlund, 2017, Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer, J. Exp. Med., 214, 579, 10.1084/jem.20162024 Biffi, 2019, IL1-induced JAK/STAT signaling is antagonized by TGFbeta to shape CAF heterogeneity in pancreatic ductal adenocarcinoma, Cancer Discov., 9, 282, 10.1158/2159-8290.CD-18-0710 Huang, 2021, Extracellular matrix and its therapeutic potential for cancer treatment, Signal. Transduct. Target Ther., 6, 153, 10.1038/s41392-021-00544-0 Nallanthighal, 2019, The role of the extracellular matrix in cancer stemness, Front Cell Dev. Biol., 7, 86, 10.3389/fcell.2019.00086 Hwang, 2019, Multiplex quantitative analysis of stroma-mediated cancer cell invasion, matrix remodeling, and drug response in a 3D co-culture model of pancreatic tumor spheroids and stellate cells, J. Exp. Clin. Cancer Res., 38, 258, 10.1186/s13046-019-1225-9 Amrutkar, 2019, Secretion of fibronectin by human pancreatic stellate cells promotes chemoresistance to gemcitabine in pancreatic cancer cells, BMC Cancer, 19, 596, 10.1186/s12885-019-5803-1 Wang, 2017, Asporin promotes pancreatic cancer cell invasion and migration by regulating the epithelial-to-mesenchymal transition (EMT) through both autocrine and paracrine mechanisms, Cancer Lett., 398, 24, 10.1016/j.canlet.2017.04.001 Liu, 2016, Periostin promotes the chemotherapy resistance to gemcitabine in pancreatic cancer, Tumour. Biol., 37, 15283, 10.1007/s13277-016-5321-6 Elahi-Gedwillo, 2019, Antifibrotic therapy disrupts stromal barriers and modulates the immune landscape in pancreatic ductal adenocarcinoma, Cancer Res., 79, 372, 10.1158/0008-5472.CAN-18-1334 Glaser, 2012, Review of MR elastography applications and recent developments, J. Magn. Reson. Imaging, 36, 757, 10.1002/jmri.23597 Maloney, 2019, Non-invasive monitoring of stromal biophysics with targeted depletion of hyaluronan in pancreatic ductal adenocarcinoma, Cancers (Basel), 11, 10.3390/cancers11060772 Ligorio, 2019, Stromal microenvironment shapes the intratumoral architecture of pancreatic cancer, Cell, 178, 160, 10.1016/j.cell.2019.05.012 Principe, 2016, TGFbeta signaling in the pancreatic tumor microenvironment promotes fibrosis and immune evasion to facilitate tumorigenesis, Cancer Res., 76, 2525, 10.1158/0008-5472.CAN-15-1293 Al-Assar, 2014, Contextual regulation of pancreatic cancer stem cell phenotype and radioresistance by pancreatic stellate cells, Radiother. Oncol., 111, 243, 10.1016/j.radonc.2014.03.014 Zhang, 2018, Tumor–stroma IL1beta–IRAK4 feedforward circuitry drives tumor fibrosis, chemoresistance, and poor prognosis in pancreatic cancer, Cancer Res., 78, 1700, 10.1158/0008-5472.CAN-17-1366 Guan, 2014, Retinoic acid inhibits pancreatic cancer cell migration and EMT through the downregulation of IL-6 in cancer associated fibroblast cells, Cancer Lett., 345, 132, 10.1016/j.canlet.2013.12.006 Zhang, 2017, Constitutive IRAK4 activation underlies poor prognosis and chemoresistance in pancreatic ductal adenocarcinoma, Clin. Cancer Res., 23, 1748, 10.1158/1078-0432.CCR-16-1121 Hu, 2022, circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis, Mol. Cancer, 21, 24, 10.1186/s12943-022-01501-3 Shi, 2019, Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring, Nature, 569, 131, 10.1038/s41586-019-1130-6 Feig, 2013, Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer, Proc. Natl. Acad. Sci. U. S. A., 110, 20212, 10.1073/pnas.1320318110 Lee, 2021, Heterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasis, Nat. Commun., 12, 7336, 10.1038/s41467-021-27607-8 Liu, 2022, Metastatic transition of pancreatic ductal cell adenocarcinoma is accompanied by the emergence of pro-invasive cancer-associated fibroblasts, Cancers (Basel), 14, 2197, 10.3390/cancers14092197 Théry, 2018, Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines, J. Extracell. Vesicles, 7, 10.1080/20013078.2018.1535750 Lopes-Rodrigues, 2017, Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles, Sci. Rep., 7, 44541, 10.1038/srep44541 Yanez-Mo, 2015, Biological properties of extracellular vesicles and their physiological functions, J. Extracell. Vesicles, 4, 27066, 10.3402/jev.v4.27066 Zhang, 2018, Micro-RNA-21 regulates cancer-associated fibroblast-mediated drug resistance in pancreatic cancer, Oncol. Res., 26, 827, 10.3727/096504017X14934840662335 Kuninty, 2016, MicroRNA-199a and -214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor, Oncotarget, 7, 16396, 10.18632/oncotarget.7651 Li, 2020, Pancreatic stellate cells derived exosomal miR-5703 promotes pancreatic cancer by downregulating CMTM4 and activating PI3K/Akt pathway, Cancer Lett., 490, 20, 10.1016/j.canlet.2020.06.009 Ma, 2020, Upregulation of exosomal microRNA21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity, Int. J. Oncol., 56, 1025 Fang, 2019, Exosomal miRNA-106b from cancer-associated fibroblast promotes gemcitabine resistance in pancreatic cancer, Exp. Cell Res., 383, 10.1016/j.yexcr.2019.111543 Han, 2022, Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer via the SCARA5–FAK axis, Cancer Biol. Ther., 23, 378, 10.1080/15384047.2022.2041961 Cao, 2021, Hypoxic pancreatic stellate cell-derived exosomal mirnas promote proliferation and invasion of pancreatic cancer through the PTEN/AKT pathway, Aging (Albany NY), 13, 7120, 10.18632/aging.202569 Chi, 2021, Exosomal lncRNA UCA1 derived from pancreatic stellate cells promotes gemcitabine resistance in pancreatic cancer via the SOCS3/EZH2 axis, Front Oncol., 11, 10.3389/fonc.2021.671082 Cheng, 2014, Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood, J. Extracell. Vesicles, 3, 23743, 10.3402/jev.v3.23743 Koga, 2011, Exosome can prevent RNase from degrading microRNA in feces, J. Gastrointest. Oncol., 2, 215 Spivak-Kroizman, 2013, Hypoxia triggers hedgehog-mediated tumor-stromal interactions in pancreatic cancer, Cancer Res., 73, 3235, 10.1158/0008-5472.CAN-11-1433 Richards, 2017, Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells, Oncogene, 36, 1770, 10.1038/onc.2016.353 Leca, 2016, Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness, J. Clin. Invest., 126, 4140, 10.1172/JCI87734 Zhao, 2016, Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism, Elife, 5, 10.7554/eLife.10250 Niederhuber, 2019 Olive, 2009, Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer, Science, 324, 1457, 10.1126/science.1171362 Xavier, 2021, Chitinase 3-like-1 and fibronectin in the cargo of extracellular vesicles shed by human macrophages influence pancreatic cancer cellular response to gemcitabine, Cancer Lett., 501, 210, 10.1016/j.canlet.2020.11.013 Nielsen, 2016, Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis, Nat. Cell Biol., 18, 549, 10.1038/ncb3340 Matsuo, 2009, CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer, Int. J. Cancer, 124, 853, 10.1002/ijc.24040 Gao, 2010, Pancreatic stellate cells increase the invasion of human pancreatic cancer cells through the stromal cell-derived factor-1/CXCR4 axis, Pancreatology, 10, 186, 10.1159/000236012 Murphy, 2019, Total neoadjuvant therapy with FOLFIRINOX in combination with losartan followed by chemoradiotherapy for locally advanced pancreatic cancer: a Phase 2 clinical trial, JAMA Oncol., 5, 1020, 10.1001/jamaoncol.2019.0892 Hingorani, 2018, HALO 202: randomized Phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine versus nab-paclitaxel/gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma, J. Clin. Oncol., 36, 359, 10.1200/JCO.2017.74.9564 Hakim, 2019, Why HALO 301 failed and implications for treatment of pancreatic cancer, Pancreas (Fairfax), 3, e1, 10.17140/POJ-3-e010 Borazanci, 2022, Phase I, first-in-human study of MSC-1 (AZD0171), a humanized anti-leukemia inhibitory factor monoclonal antibody, for advanced solid tumors, ESMO Open, 7, 10.1016/j.esmoop.2022.100530 O'Kane, 2022, Abstract CT126: a phase 2 trial of first-line AZD0171 + durvalumab and chemotherapy (CT) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and CD8+ T cell infiltration, Cancer Res., 82, 10.1158/1538-7445.AM2022-CT126 Melisi, 2019, TGFbeta receptor inhibitor galunisertib is linked to inflammation- and remodeling-related proteins in patients with pancreatic cancer, Cancer Chemother. Pharmacol., 83, 975, 10.1007/s00280-019-03807-4 Pijnappel, 2021, Phase I/II study of LDE225 in combination with gemcitabine and Nab-paclitaxel in patients with metastatic pancreatic cancer, Cancers (Basel), 13, 4869, 10.3390/cancers13194869 Steele, 2021, Inhibition of Hedgehog signaling alters fibroblast composition in pancreatic cancer, Clin. Cancer Res., 27, 2023, 10.1158/1078-0432.CCR-20-3715 Rhim, 2014, Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma, Cancer Cell, 25, 735, 10.1016/j.ccr.2014.04.021 Lo, 2015, Tumor-promoting desmoplasia is disrupted by depleting FAP-expressing stromal cells, Cancer Res., 75, 2800, 10.1158/0008-5472.CAN-14-3041 Mizutani, 2019, Meflin-positive cancer-associated fibroblasts inhibit pancreatic carcinogenesis, Cancer Res., 79, 5367, 10.1158/0008-5472.CAN-19-0454 Sherman, 2014, Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy, Cell, 159, 80, 10.1016/j.cell.2014.08.007 Grierson, 2022, A pilot study of liposomal irinotecan plus 5-FU/LV combined with paricalcitol in patients with advanced pancreatic cancer which progressed on gemcitabine-based therapy, J. Clin. Oncol., 40, 566, 10.1200/JCO.2022.40.4_suppl.566 Kocher, 2020, Phase I clinical trial repurposing all-trans retinoic acid as a stromal targeting agent for pancreatic cancer, Nat. Commun., 11, 4841, 10.1038/s41467-020-18636-w Mizutani, 2022, Safety and efficacy of MIKE-1 in patients with advanced pancreatic cancer: a study protocol for an open-label phase I/II investigator-initiated clinical trial based on a drug repositioning approach that reprograms the tumour stroma, BMC Cancer, 22, 205, 10.1186/s12885-022-09272-2 Iida, 2022, Pharmacologic conversion of cancer-associated fibroblasts from a protumor phenotype to an antitumor phenotype improves the sensitivity of pancreatic cancer to chemotherapeutics, Oncogene, 41, 2764, 10.1038/s41388-022-02288-9 Wang, 2021, Blood-based extracellular matrix biomarkers as predictors of survival in patients with metastatic pancreatic ductal adenocarcinoma receiving pegvorhyaluronidase alfa, J. Transl. Med., 19, 39, 10.1186/s12967-021-02701-z Nissen, 2022, Collagen biomarkers quantify fibroblast activity in vitro and predict survival in patients with pancreatic ductal adenocarcinoma, Cancers (Basel), 14, 819, 10.3390/cancers14030819 Dings, 2023, Serum levels of iCAF-derived osteoglycin predict favorable outcome in pancreatic cancer, Int. J. Cancer, 152, 511, 10.1002/ijc.34276 Miyazaki, 2022, Potential metabolite markers for pancreatic cancer identified by metabolomic analysis of induced cancer-associated fibroblasts, Cancers (Basel), 14, 1375, 10.3390/cancers14061375 Neuzillet, 2019, Inter- and intra-tumoural heterogeneity in cancer-associated fibroblasts of human pancreatic ductal adenocarcinoma, J. Pathol., 248, 51, 10.1002/path.5224 International Society for Extracellular Vesicles. https://www.isev.org/ Barbosa, 2021, 3D cell culture models as recapitulators of the tumor microenvironment for the screening of anti-cancer drugs, Cancers (Basel), 14, 190, 10.3390/cancers14010190 Pandol, 2009, Desmoplasia of pancreatic ductal adenocarcinoma, Clin. Gastroenterol. Hepatol., 7, S44, 10.1016/j.cgh.2009.07.039 Neesse, 2011, Stromal biology and therapy in pancreatic cancer, Gut, 60, 861, 10.1136/gut.2010.226092 Provenzano, 2012, Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma, Cancer Cell, 21, 418, 10.1016/j.ccr.2012.01.007 Erkan, 2013, The role of pancreatic stellate cells in pancreatic cancer, Pancreatology, 13, 106, 10.1016/j.pan.2013.01.008 Erkan, 2007, Periostin creates a tumor-supportive microenvironment in the pancreas by sustaining fibrogenic stellate cell activity, Gastroenterology, 132, 1447, 10.1053/j.gastro.2007.01.031 Erkan, 2012, The role of stroma in pancreatic cancer: diagnostic and therapeutic implications, Nat. Rev. Gastroenterol. Hepatol., 9, 454, 10.1038/nrgastro.2012.115 Aichler, 2012, Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: a comparative study in transgenic mice and human tissues, J. Pathol., 226, 723, 10.1002/path.3017 Xing, 2010, Cancer associated fibroblasts (CAFs) in tumor microenvironment, Front Biosci. (Landmark Ed), 15, 166, 10.2741/3613 Li, 2007, Tumor microenvironment: the role of the tumor stroma in cancer, J. Cell. Biochem., 101, 805, 10.1002/jcb.21159 Sahai, 2020, A framework for advancing our understanding of cancer-associated fibroblasts, Nat. Rev. Cancer, 20, 174, 10.1038/s41568-019-0238-1 Dvorak, 2015, Tumors: wounds that do not heal – redux, Cancer Immunol. Res., 3, 1, 10.1158/2326-6066.CIR-14-0209 Vonlaufen, 2008, Pancreatic stellate cells: partners in crime with pancreatic cancer cells, Cancer Res., 68, 2085, 10.1158/0008-5472.CAN-07-2477 Fukino, 2004, Combined total genome loss of heterozygosity scan of breast cancer stroma and epithelium reveals multiplicity of stromal targets, Cancer Res., 64, 7231, 10.1158/0008-5472.CAN-04-2866 Quante, 2011, Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth, Cancer Cell, 19, 257, 10.1016/j.ccr.2011.01.020 Waghray, 2016, GM-CSF mediates mesenchymal–epithelial cross-talk in pancreatic cancer, Cancer Discov., 6, 886, 10.1158/2159-8290.CD-15-0947 Zeisberg, 2007, Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts, Cancer Res., 67, 10123, 10.1158/0008-5472.CAN-07-3127 Han, 2020, Biomarkers for cancer-associated fibroblasts, Biomark Res., 8, 64, 10.1186/s40364-020-00245-w Geng, 2021, Cancer-associated fibroblast (CAF) heterogeneity and targeting therapy of CAFs in pancreatic cancer, Front Cell Dev. Biol., 9, 10.3389/fcell.2021.655152 Bernard, 2019, Single-cell transcriptomics of pancreatic cancer precursors demonstrates epithelial and microenvironmental heterogeneity as an early event in neoplastic progression, Clin. Cancer Res., 25, 2194, 10.1158/1078-0432.CCR-18-1955 Hosein, 2019, Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution, JCI Insight, 5 Dominguez, 2020, Single-cell RNA sequencing reveals stromal evolution into LRRC15+ myofibroblasts as a determinant of patient response to cancer immunotherapy, Cancer Discov., 10, 232, 10.1158/2159-8290.CD-19-0644 Boyd, 2022, Heterogeneity and plasticity of cancer-associated fibroblasts in the pancreatic tumor microenvironment, Semin. Cancer Biol., 82, 184, 10.1016/j.semcancer.2021.03.006 Zhan, 2017, Crosstalk between stromal cells and cancer cells in pancreatic cancer: new insights into stromal biology, Cancer Lett., 392, 83, 10.1016/j.canlet.2017.01.041 Froeling, 2011, Retinoic acid-induced pancreatic stellate cell quiescence reduces paracrine Wnt–beta-catenin signaling to slow tumor progression, Gastroenterology, 141, 1486, 10.1053/j.gastro.2011.06.047 Sarper, 2016, ATRA modulates mechanical activation of TGF-beta by pancreatic stellate cells, Sci. Rep., 6, 27639, 10.1038/srep27639 Allam, 2017, Pancreatic stellate cells in pancreatic cancer: In focus, Pancreatology, 17, 514, 10.1016/j.pan.2017.05.390 Roy, 2017, Cancer cell chemokines direct chemotaxis of activated stellate cells in pancreatic ductal adenocarcinoma, Lab. Investig., 97, 302, 10.1038/labinvest.2016.146 Fu, 2018, The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma, Mol. Cancer, 17, 62, 10.1186/s12943-018-0815-z Hanahan, 2022, Hallmarks of cancer: new dimensions, Cancer Discov., 12, 31, 10.1158/2159-8290.CD-21-1059 Faget, 2019, Unmasking senescence: context-dependent effects of SASP in cancer, Nat. Rev. Cancer, 19, 439, 10.1038/s41568-019-0156-2 Takikawa, 2022, Senescent human pancreatic stellate cells secrete CXCR2 agonist CXCLs to promote proliferation and migration of human pancreatic cancer AsPC-1 and MIAPaCa-2 cell lines, Int. J. Mol. Sci., 23, 9275, 10.3390/ijms23169275 Peng, 2013, Biological characteristics and genetic heterogeneity between carcinoma-associated fibroblasts and their paired normal fibroblasts in human breast cancer, PLoS One, 8 Wang, 2017, Senescent carcinoma-associated fibroblasts upregulate IL8 to enhance prometastatic phenotypes, Mol. Cancer Res., 15, 3, 10.1158/1541-7786.MCR-16-0192 Yamao, 2019, Cellular senescence, represented by expression of caveolin-1, in cancer-associated fibroblasts promotes tumor invasion in pancreatic cancer, Ann. Surg. Oncol., 26, 1552, 10.1245/s10434-019-07266-2