Cancer-associated fibroblasts and their significance in tumor progression

Close metadata

Recommended articles:

Analysis of the work of the Immunohistochemical Quality Control Center of the Russian Medical Academy of Continuous Professional Education of the Ministry of Health of Russia in 2023. Russian Journal of Archive of Pathology. 2024;(3):38-45

The role of immunohistochemical examination in the differential diagnosis of atypical tumors and carcinomas of parathyroid glands. Russian Journal of Archive of Pathology. 2024;(4):5-12

Alveolar adenoma of the lung. Russian Journal of Archive of Pathology. 2024;(4):38-41

Risk groups model in colorectal cancer screening. Russian Journal of Preventive Medicine. 2024;(5):12-22

Influence of intestinal microbiota on cardiovascular atherosclerotic diseases and colorectal cancer in elderly patients. Regenerative Biotechnologies, Preventive, Digital and Predictive Medicine. 2024;(1):30-36

Metastatic lesion of lymph nodes in papillary thyroid cancer on the background of autoimmune thyroiditis. P.A. Herzen Journal of Oncology. 2024;(3):27-33

Palliative large-bowel decompression for colorectal obstruction in patients with unresectable locally advanced cancer and carcinomatosis. Endoscopic Surgery. 2024;(3):21-28

Primary prevention of colorectal cancer and technologies for its implementation into practical health care. Russian Journal of Preventive Medicine. 2024;(6):111-117

Comparative analysis of combined treatment methods for patients with single brain lesions. Burdenko's Journal of Neurosurgery. 2024;(4):13-21

Melanoma metastasis to the brachial plexus and median nerve. A rare clinical case. Burdenko's Journal of Neurosurgery. 2024;(5):93-101

Carcinogenesis and tumor progression are not caused not only by malignant epithelial cells, but also by the tumor stroma around cancer stem cells which performs regulatory, nutritional and «framework» functions. It is represented by mesenchymal cells of various types predominantly by cancer-associated fibroblasts (CAF). αSMA, FAP-1, desmin, podoplanin, neuron-glial antigen 2 (NG2), PDGFR-α and -β are used for CAF identification but there is no universal markers due to the plasticity of the cell population that underlies the subpopulation division CAF. CAF subpopulations are not described for many tumor types. Recently, evidence has accumulated that CAFs mediate many adverse processes in the tumor, including can support stromal inflammation and cause fibrosis. By forming a niche in cancer stem cells, CAFs mediate chemoresistance and the appearance of dormant metastases. The study of the role of CAF will allow not only to form a fundamentally new understanding of the mechanisms of carcinogenesis, but also to create new diagnostic and therapeutic targets for treating tumors.

Keywords:

colorectal cancer

cancer stem cells

cancer-associated fibroblasts

metastasis

immunohistochemistry

Authors:

Oleynikova N.А.

Lomonosov Moscow State University, Moscow, Russia

Danilova N.V.

FGBU "Moskovskiĭ nauchno-issledovatel'skiĭ onkologicheskiĭ institut im. P.A. Gertsena" Minzdrava RF;
GBOU DPO "Rossiĭskaia meditsinskaia akademiia poslediplomnogo obrazovaniia", Moskva

Mikhailov I.A.

Lomonosov Moscow State University

SPIN RSCI: 5798-0749
Scopus AuthorID: 57203900904
ResearcherID: I-9035-2017
ORCID: 0000-0001-8020-369X

Semina E.V.

M.V. Lomonosov Moscow State University, Moscow, Russia;
National Medical Research Center for Cardiology, Ministry of Health of Russia, Moscow, Russia

Mal'kov P.G.

GUNU "Fakul'tet fundamental'noĭ meditsiny MGU im. M.V. Lomonosova";
GBOU DPO "Rossiĭskaia meditsinskaia akademiia poslediplomnogo obrazovaniia", Moskva

List of references:

Huang Y, Zhou S, Huang Y, Zheng D, Mao Q, He J, Wang Y, Xue D, Lu X, Yang N, Zhao Y. Isolation of Fibroblast-Activation Protein-Specific Cancer-Associated Fibroblasts. Biomed Res Int. 2017;2017:4825108. https://doi.org/10.1155/2017/4825108
Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16(9):582-598. https://doi.org/10.1038/nrc.2016.73
Tommelein J, Verset L, Boterberg T, Demetter P, Bracke M, De Wever O. Cancer-associated fibroblasts connect metastasis-promoting communication in colorectal cancer. Front Oncol. 2015;5:63. https://doi.org/10.3389/fonc.2015.00063
Alkasalias T, Moyano-Galceran L, Arsenian-Henriksson M, Lehti K. Fibroblasts in the tumor microenvironment: shield or spear? Int J Mol Sci. 2018;19(5). pii: E1532. https://doi.org/10.3390/ijms19051532
Abdollahi A, Hahnfeldt P, Maercker C, Grone HJ, Debus J, Ansorge W, Folkman J, Hlatky L, Huber PE. Endostatin’s antiangiogenic signaling network. Mol Cell. 2004;13(5):649-463.
Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Takeyama H. Cancer-Associated Fibroblasts: their characteristics and their roles in tumor growth. Cancers. 2015;7(4):2443-2458. https://doi.org/10.3390/cancers7040902
Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle. 2009;8(23):3984-4001. https://doi.org/10.4161/cc.8.23.10238
Ishii G, Ochiai A, Neri S. Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment. Adv Drug Deliv Rev. 2016;99(Pt B):186-196. https://doi.org/10.1016/j.addr.2015.07.007
Berdiel-Acer M, Sanz-Pamplona R, Calon A, Cuadras D, Berenguer A, Sanjuan X, Paules MJ, Salazar R, Moreno V, Batlle E, Villanueva A, Mollevi DG. Differences between CAFs and their paired NCF from adjacent colonic mucosa reveal functional heterogeneity of CAFs, providing prognostic information. Mol Oncol. 2014;8(7):1290-1305. https://doi.org/10.1016/j.molonc.2014.04.006
Bauer M, Su G, Casper C, He R, Rehrauer W, Friedl A. Heterogeneity of gene expression in stromal fibroblasts of human breast carcinomas and normal breast. Oncogene. 2010;29(12):1732-1740. https://doi.org/10.1038/onc.2009.463
Navab R, Strumpf D, Bandarchi B, Zhu CQ, Pintilie M, Ramnarine VR, Ibrahimov E, Radulovich N, Leung L, Barczyk M, Panchal D, To C, Yun JJ, Der S, Shepherd FA, Jurisica I, Tsao MS. Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer. Proc Natl Acad Sci USA. 2011;108(17):7160-7165. https://doi.org/10.1073/pnas.1014506108
Zhang C, Fu L, Fu J, Hu L, Yang H, Rong TH, Li Y, Liu H, Fu SB, Zeng YX, Guan XY. Fibroblast growth factor receptor 2-positive fibroblasts provide a suitable microenvironment for tumor development and progression in esophageal carcinoma. Clin Cancer Res. 2009;15(12):4017-4027. https://doi.org/10.1158/1078-0432.CCR-08-2824
Dumont N, Liu B, Defilippis RA, Chang H, Rabban JT, Karnezis AN, Tjoe JA, Marx J, Parvin B, Tlsty TD. Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics. Neoplasia. 2013;15(3):249-462. https://doi.org/10.1593/neo.121950
Folkman J, Kalluri R. Cancer without disease. Nature. 2004; 427(6977):787. https://doi.org/10.1038/427787a
Darby IA, Laverdet B, Bonte F, Desmouliere A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;7:301-311. https://doi.org/10.2147/CCID.S50046
Cortez E, Roswall P, Pietras K. Functional subsets of mesenchymal cell types in the tumor microenvironment. Semin Cancer Biol. 2014;25:3-9. https://doi.org/10.1016/j.semcancer.2013.12.010
Folgueira MA, Maistro S, Katayama ML, Roela RA, Mundim FG, Nanogaki S, de Bock GH, Brentani MM. Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series. Biosci Rep. 2013;33(6).pii:e00085. https://doi.org/10.1042/BSR20130060
Herrera M, Herrera A, Dominguez G, Silva J, Garcia V, Garcia JM, Gomez I, Soldevilla B, Munoz C, Provencio M, Campos-Martin Y, Garcia de Herreros A, Casal I, Bonilla F, Pena C. Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients. Cancer Sci. 2013;104(4):437-444. https://doi.org/10.1111/cas.12096
Kilvaer TK, Rakaee M, Hellevik T, Ostman A, Strell C, Bremnes RM, Busund LT, Donnem T, Martinez-Zubiaurre I. Tissue analyses reveal a potential immune-adjuvant function of FAP-1 positive fibroblasts in non-small cell lung cancer. PloS One. 2018; 13(2):e0192157. https://doi.org/10.1371/journal.pone.0192157
Flaberg E, Markasz L, Petranyi G, Stuber G, Dicso F, Alchihabi N, Olah E, Csizy I, Jozsa T, Andren O, Johansson JE, Andersson SO, Klein G, Szekely L. High-throughput live-cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts. Int J Cancer. 2011;128(12):2793-2802. https://doi.org/10.1002/ijc.25612
Takahashi A, Ishii G, Neri S, Yoshida T, Hashimoto H, Suzuki S, Umemura S, Matsumoto S, Yoh K, Niho S, Goto K, Ohmatsu H, Nagai K, Gemma A, Ohe Y, Ochiai A. Podoplanin-expressing cancer-associated fibroblasts inhibit small cell lung cancer growth. Oncotarget. 2015;6(11):9531-9541. https://doi.org/10.18632/oncotarget.3371
Choi SY, Sung R, Lee SJ, Lee TG, Kim N, Yoon SM, Lee EJ, Chae HB, Youn SJ, Park SM. Podoplanin, alpha-smooth muscle actin or S100A4 expressing cancer-associated fibroblasts are associated with different prognosis in colorectal cancers. J Korean Med Sci. 2013;28(9):1293-1301. https://doi.org/10.3346/jkms.2013.28.9.1293
Park CK, Jung WH, Koo JS. Expression of cancer-associated fibroblast-related proteins differs between invasive lobular carcinoma and invasive ductal carcinoma. Breast Cancer Res Treat. 2016;159(1):55-69. https://doi.org/10.1007/s10549-016-3929-2
Chen Y, Zou L, Zhang Y, Chen Y, Xing P, Yang W, Li F, Ji X, Liu F, Lu X. Transforming growth factor-beta1 and alpha-smooth muscle actin in stromal fibroblasts are associated with a poor prognosis in patients with clinical stage I-IIIA nonsmall cell lung cancer after curative resection. Tumour Biol. 2014;35(7):6707-6713. https://doi.org/10.1007/s13277-014-1908-y
Ishikawa S, Takenaka K, Yanagihara K, Miyahara R, Kawano Y, Otake Y, Hasegawa S, Wada H, Tanaka F. Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell lung cancer. Clin Cancer Res. 2004;10(19):6579-6585. https://doi.org/10.1158/1078-0432.CCR-04-0272
Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld RA. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PloS One. 2009;4(11):e7965. https://doi.org/10.1371/journal.pone.0007965
Edlund K, Lindskog C, Saito A, Berglund A, Ponten F, Goransson-Kultima H, Isaksson A, Jirstrom K, Planck M, Johansson L, Lambe M, Holmberg L, Nyberg F, Ekman S, Bergqvist M, Landelius P, Lamberg K, Botling J, Ostman A, Micke P. CD99 is a novel prognostic stromal marker in non-small cell lung cancer. Int J Cancer. 2012;131(10):2264-2273. https://doi.org/10.1002/ijc.27518
Henry LR, Lee HO, Lee JS, Klein-Szanto A, Watts P, Ross EA, Chen WT, Cheng JD. Clinical implications of fibroblast activation protein in patients with colon cancer. Clin Cancer Res. 2007;13(6):1736-1741. https://doi.org/10.1158/1078-0432.CCR-06-1746
Kilvaer TK, Khanehkenari MR, Hellevik T, Al-Saad S, Paulsen EE, Bremnes RM, Busund LT, Donnem T, Martinez IZ. Cancer Associated Fibroblasts in Stage I-IIIA NSCLC: Prognostic impact and their correlations with tumor molecular markers. PloS One. 2015;10(8):e0134965. https://doi.org/10.1371/journal.pone.0134965
Kitano H, Kageyama S, Hewitt SM, Hayashi R, Doki Y, Ozaki Y, Fujino S, Takikita M, Kubo H, Fukuoka J. Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient survival. Arch Pathol Lab Med. 2010;134(10):1520-1527.
Leinonen T, Pirinen R, Bohm J, Johansson R, Kosma VM. Increased expression of matrix metalloproteinase-2 (MMP-2) predicts tumour recurrence and unfavourable outcome in non-small cell lung cancer. Histol Histopathol. 2008;23(6):693-700. https://doi.org/10.14670/HH-23.693
Al-Saad S, Al-Shibli K, Donnem T, Persson M, Bremnes RM, Busund LT. The prognostic impact of NF-kappaB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer. Br J Cancer. 2008;99(9):1476-1483. https://doi.org/10.1038/sj.bjc.6604713
Shu H, Li HF. Prognostic effect of stromal myofibroblasts in lung adenocarcinoma. Neoplasma. 2012;59(6):658-661. https://doi.org/10.4149/neo_2012_083
Ito M, Ishii G, Nagai K, Maeda R, Nakano Y, Ochiai A. Prognostic impact of cancer-associated stromal cells in patients with stage I lung adenocarcinoma. Chest. 2012;142(1):151-158. https://doi.org/10.1378/chest.11-2458
Kawase A, Ishii G, Nagai K, Ito T, Nagano T, Murata Y, Hishida T, Nishimura M, Yoshida J, Suzuki K, Ochiai A. Podoplanin expression by cancer associated fibroblasts predicts poor prognosis of lung adenocarcinoma. Int J Cancer. 2008;123(5):1053-1059. https://doi.org/10.1002/ijc.23611
Koriyama H, Ishii G, Yoh K, Neri S, Morise M, Umemura S, Matsumoto S, Niho S, Ohmatsu H, Tsuboi M, Goto K, Ochiai A. Presence of podoplanin-positive cancer-associated fibroblasts in surgically resected primary lung adenocarcinoma predicts a shorter progression-free survival period in patients with recurrences who received platinum-based chemotherapy. J Cancer Res Clin Oncol. 2015;141(7):1163-1170. https://doi.org/10.1007/s00432-014-1891-0
Neri S, Ishii G, Taira T, Hishida T, Yoshida J, Nishimura M, Nagai K, Ochiai A. Recruitment of podoplanin positive cancer-associated fibroblasts in metastatic lymph nodes predicts poor prognosis in pathological N2 stage III lung adenocarcinoma. Ann Surg Oncol. 2012;19(12):3953-3962. https://doi.org/10.1245/s10434-012-2421-4
Ono S, Ishii G, Nagai K, Takuwa T, Yoshida J, Nishimura M, Hishida T, Aokage K, Fujii S, Ikeda N, Ochiai A. Podoplanin-positive cancer-associated fibroblasts could have prognostic value independent of cancer cell phenotype in stage I lung squamous cell carcinoma: usefulness of combining analysis of both cancer cell phenotype and cancer-associated fibroblast phenotype. Chest. 2013;143(4):963-970. https://doi.org/10.1378/chest.12-0913
Schoppmann SF, Berghoff A, Dinhof C, Jakesz R, Gnant M, Dubsky P, Jesch B, Heinzl H, Birner P. Podoplanin-expressing cancer-associated fibroblasts are associated with poor prognosis in invasive breast cancer. Breast Cancer Res Treat. 2012;134(1):237-324. https://doi.org/10.1007/s10549-012-1984-x
Pula B, Jethon A, Piotrowska A, Gomulkiewicz A, Owczarek T, Calik J, Wojnar A, Witkiewicz W, Rys J, Ugorski M, Dziegiel P, Podhorska-Okolow M. Podoplanin expression by cancer-associated fibroblasts predicts poor outcome in invasive ductal breast carcinoma. Histopathology. 2011;59(6):1249-1260. https://doi.org/10.1111/j.1365-2559.2011.04060.x
Yamanashi T, Nakanishi Y, Fujii G, Akishima-Fukasawa Y, Moriya Y, Kanai Y, Watanabe M, Hirohashi S. Podoplanin expression identified in stromal fibroblasts as a favorable prognostic marker in patients with colorectal carcinoma. Oncology. 2009;77(1):53-62. https://doi.org/10.1159/000226112
Sandberg TP, Stuart M, Oosting J, Tollenaar R, Sier CFM, Mesker WE. Increased expression of cancer-associated fibroblast markers at the invasive front and its association with tumor-stroma ratio in colorectal cancer. BMC Cancer. 2019;19(1):284. https://doi.org/10.1186/s12885-019-5462-2
Son GM, Kwon MS, Shin DH, Shin N, Ryu D, Kang CD. Comparisons of cancer-associated fibroblasts in the intratumoral stroma and invasive front in colorectal cancer. Medicine (Baltimore). 2019;98(18):e15164. https://doi.org/10.1097/MD.0000000000015164
Carvalho FM, Zaganelli FL, Almeida BG, Goes JC, Baracat EC, Carvalho JP. Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas. Clinics. 2010;65(12):1279-1283. https://doi.org/10.1590/s1807-59322010001200009
Kan S, Konishi E, Arita T, Ikemoto C, Takenaka H, Yanagisawa A, Katoh N, Asai J. Podoplanin expression in cancer-associated fibroblasts predicts aggressive behavior in melanoma. J Cutan Pathol. 2014;41(7):561-567. https://doi.org/10.1111/cup.12322
Aishima S, Nishihara Y, Iguchi T, Taguchi K, Taketomi A, Maehara Y, Tsuneyoshi M. Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma. Mod Pathol. 2008;21(3):256-264. https://doi.org/10.1038/modpathol.3800985
Schoppmann SF, Jesch B, Riegler MF, Maroske F, Schwameis K, Jomrich G, Birner P. Podoplanin expressing cancer associated fibroblasts are associated with unfavourable prognosis in adenocarcinoma of the esophagus. Clin Exp Metastasis. 2013;30(4):441-446. https://doi.org/10.1007/s10585-012-9549-2
Nishishita R, Morohashi S, Seino H, Wu Y, Yoshizawa T, Haga T, Saito K, Hakamada K, Fukuda S, Kijima H. Expression of cancer-associated fibroblast markers in advanced colorectal cancer. Oncol Lett. 2018;15(5):6195-6202. https://doi.org/10.3892/ol.2018.8097
Pula B, Witkiewicz W, Dziegiel P, Podhorska-Okolow M. Significance of podoplanin expression in cancer-associated fibroblasts: a comprehensive review. Int J Oncol. 2013;42(6):1849-1857. https://doi.org/10.3892/ijo.2013.1887
Quintanilla M, Montero-Montero L, Renart J, Martin-Villar E. Podoplanin in inflammation and cancer. Int J Mol Sci. 2019;20(3): pii: E707. https://doi.org/10.3390/ijms20030707
Krishnan H, Ochoa-Alvarez JA, Shen Y, Nevel E, Lakshminarayanan M, Williams MC, Ramirez MI, Miller WT, Goldberg GS. Serines in the intracellular tail of podoplanin (PDPN) regulate cell motility. J Biol Chem. 2013;288(17):12215-12221. https://doi.org/10.1074/jbc.C112.446823
Ordonez NG. Value of podoplanin as an immunohistochemical marker in tumor diagnosis: a review and update. Appl Immunohistochem Mol Morphol. 2014;22(5):331-347. https://doi.org/10.1097/PAI.0b013e31828a83c5
Hoshino A, Ishii G, Ito T, Aoyagi K, Ohtaki Y, Nagai K, Sasaki H, Ochiai A. Podoplanin-positive fibroblasts enhance lung adenocarcinoma tumor formation: podoplanin in fibroblast functions for tumor progression. Cancer Res. 2011;71(14):4769-4779. https://doi.org/10.1158/0008-5472.CAN-10-3228
Nakayama H, Enzan H, Yasui W. Expression of podoplanin/D2-40 in pericryptal stromal cells in superficial colorectal epithelial neoplasia. Med Mol Morphol. 2013;46(1):20-23. https://doi.org/10.1007/s00795-012-0004-x
Huang L, Xu AM, Liu S, Liu W, Li TJ. Cancer-associated fibroblasts in digestive tumors. World J Gastroenterol. 2014;20(47):17804-17818. https://doi.org/10.3748/wjg.v20.i47.17804
Scherz-Shouval R, Santagata S, Mendillo ML, Sholl LM, Ben-Aharon I, Beck AH, Dias-Santagata D, Koeva M, Stemmer SM, Whitesell L, Lindquist S. The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy. Cell. 2014;158(3):564-578. https://doi.org/10.1016/j.cell.2014.05.045
O’Connell JT, Sugimoto H, Cooke VG, MacDonald BA, Mehta AI, LeBleu VS, Dewar R, Rocha RM, Brentani RR, Resnick MB, Neilson EG, Zeisberg M, Kalluri R. VEGF-A and Tenascin-C produced by S100A4+ stromal cells are important for metastatic colonization. Proc Natl Acad Sci USA. 2011;108(38):16002-16007. https://doi.org/10.1073/pnas.1109493108
Olaso E, Santisteban A, Bidaurrazaga J, Gressner AM, Rosenbaum J, Vidal-Vanaclocha F. Tumor-dependent activation of rodent hepatic stellate cells during experimental melanoma metastasis. Hepatology. 1997;26(3):634-642. https://doi.org/10.1002/hep.510260315
Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Cespedes MV, Sevillano M, Nadal C, Jung P, Zhang XH, Byrom D, Riera A, Rossell D, Mangues R, Massague J, Sancho E, Batlle E. Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for metastasis initiation. Cancer Cell. 2012;22(5):571-584. https://doi.org/10.1016/j.ccr.2012.08.013
Duda DG, Duyverman AM, Kohno M, Snuderl M, Steller EJ, Fukumura D, Jain RK. Malignant cells facilitate lung metastasis by bringing their own soil. Proc Natl Acad Sci USA. 2010;107(50):21677-21682. https://doi.org/10.1073/pnas.1016234107
Tsujino T, Seshimo I, Yamamoto H, Ngan CY, Ezumi K, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M. Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clin Cancer Res. 2007;13(7):2082-2090. https://doi.org/10.1158/1078-0432.CCR-06-2191
Kwak Y, Lee HE, Kim WH, Kim DW, Kang SB, Lee HS. The clinical implication of cancer-associated microvasculature and fibroblast in advanced colorectal cancer patients with synchronous or metachronous metastases. PloS One. 2014;9(3):e91811. https://doi.org/10.1371/journal.pone.0091811
Jiang GM, Xu W, Du J, Zhang KS, Zhang QG, Wang XW, Liu ZG, Liu SQ, Xie WY, Liu HF, Liu JS, Wu BP. The application of the fibroblast activation protein alpha-targeted immunotherapy strategy. Oncotarget. 2016;7(22):33472-33482. https://doi.org/10.18632/oncotarget.8098
Yoshida T, Ishii G, Goto K, Neri S, Hashimoto H, Yoh K, Niho S, Umemura S, Matsumoto S, Ohmatsu H, Iida S, Niimi A, Nagai K, Ohe Y, Ochiai A. Podoplanin-positive cancer-associated fibroblasts in the tumor microenvironment induce primary resistance to EGFR-TKIs in lung adenocarcinoma with EGFR mutation. Clinl Cancer Res. 2015;21(3):642-651. https://doi.org/10.1158/1078-0432.CCR-14-0846
Ohlund D, Elyada E, Tuveson D. Fibroblast heterogeneity in the cancer wound. J Exp Med. 2014;211(8):1503-1523. https://doi.org/10.1084/jem.20140692
Loeffler M, Kruger JA, Niethammer AG, Reisfeld RA. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J Clin Invest. 2006;116(7):1955-1962. https://doi.org/10.1172/JCI26532
Mertens JC, Fingas CD, Christensen JD, Smoot RL, Bronk SF, Werneburg NW, Gustafson MP, Dietz AB, Roberts LR, Sirica AE, Gores GJ. Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma. Cancer Res. 2013;73(2):897-907. https://doi.org/10.1158/0008-5472.CAN-12-2130

Close metadata