The Importance of Cancer-Associated Fibroblasts in the Pathogenesis of Head and Neck Cancers


Authors: Martina Raudenská 1;  Markéta Svobodová 2;  Jaromír Gumulec 2;  Martin Falk 3;  Michal Masařík 1,2,4
Authors‘ workplace: Fyziologický ústav, LF MU, Brno 1;  Ústav patologické fyziologie, LF MU, Brno 2;  Biofyzikální ústav AV ČR, v. v. i., Brno 3;  1. LF UK a BIOCEV – Biotechnologické a biomedicínské centrum AV ČR, v. v. i., Vestec 4
Published in: Klin Onkol 2020; 33(1): 39-48
Category: Review
doi: 10.14735/amko202039

Overview

Background: Despite progress in anticancer therapies, head and neck squamous cell carcinoma (HNSCC) has still a low survival rate. Recent studies have shown that tumour stroma may play an important role in the pathogenesis of this malignant disease. Fibroblasts are a major component of the tumour microenvironment and may significantly influence HNSCC progression as indicated by the contribution they make to important hallmarks of cancer, such as inflammation, non-restricted growth, angiogenesis, invasion, metastasis, and therapy resistance. It is well known that tumour cells can confer a cancer-associated fibroblast (CAF) phenotype that supports the growth and dissemination of cancer cells. CAFs can stimulate cancer progression through cell-cell contacts and communication, remodelling of extracellular matrix, and production of many signal molecules and matrix metalloproteinases. Consequently, genetic changes in epithelial cells are probably not the only factor that drives HNSCC carcinogenesis. Non-genetic changes in the tumour stroma can also be significantly involved. Stress-induced signals can induce a multicellular program, creating a field of tissue that is predisposed to malignant transformation. The “field cancerization” concept represents a process of active evolution of intercellular interactions and feedback loops between tumour and stromal cells. This model paves the way to study cancer from a new perspective and identify new therapeutic targets.

Purpose: In this review, we discuss current knowledge about CAFs, such as their cellular origin, phenotypical plasticity and functional heterogeneity, and stress their contribution to HNSCC progression.

This article was supported by the project AZV 16-29835A.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted: 18. 6. 2019

Accepted: 9. 9. 2019

Keywords:

extracellular matrix – Angiogenesis – head and neck squamous cell carcinoma – cancer-associated fibroblasts – cancer microenvironment – neoplasm metastasis


Sources

1. Lemaire F, Millon R, Young J et al. Differential expression profiling of head and neck squamous cell carcinoma (HNSCC). Br J Cancer 2003; 89 (10): 1940–1949. doi: 10.1038/sj.bjc.6601373.

2. Duray A, Demoulin S, Hubert P et al. Immune suppression in head and neck cancers: a review. Clin Dev Immunol 2010; 2010: 701657. doi: 10.1155/2010/701657.

3. Castells M, Thibault B, Delord JP et al. Implication of tumor microenvironment in chemoresistance: tumor-associated stromal cells protect tumor cells from cell death. Int J Mol Sci 2012; 13 (8): 9545–9571. doi: 10.3390/ijms13089545.

4. Meads MB, Gatenby RA, Dalton WS. Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer 2009; 9 (9): 665–674. doi: 10.1038/nrc2714.

5. Rautava J, Syrjänen S. Biology of human papillomavirus infections in head and neck carcinogenesis. Head Neck Pathol 2012; 6 (Suppl 1): S3–S15. doi: 10.1007/s12105-012-0367-2.

6. Kalluri R. Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer 2003; 3 (6): 422–433. doi: 10.1038/nrc1094.

7. Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer 2016; 16 (9): 582–598. doi: 10.1038/nrc.2016.73.

8. Nurmik M, Ullmann P, Rodriguez F et al. In search of definitions: cancer-associated fibroblasts and their markers. Int J Cancer 2019. doi: 10.1002/ijc.32193.

9. Österreicher CH, Penz-Österreicher M, Grivennikov SI et al. Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver. Proc Natl Acad Sci USA 2011; 108 (1): 308–313. doi: 10.1073/pnas.1017547108.

10. Kahounova Z, Kurfurstova D, Bouchal J et al. The fibroblast surface markers FAP, anti-fibroblast, and FSP are expressed by cells of epithelial origin and may be altered during epithelial-to-mesenchymal transition. Cytometry A 2018; 93 (9): 941–951. doi: 10.1002/cyto.a.23101.

11. Gabbiani G, Ryan GB, Majne G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 1971; 27 (5): 549–550. doi: 10.1007/bf02147594.

12. Desmouliere A, Darby IA, Gabbiani G. Normal and pathologic soft tissue remodeling: role of the myofibroblast, with special emphasis on liver and kidney fibrosis. Lab Invest 2003; 83 (12): 1689–1707. doi: 10.1097/01.lab.0000101911.53973.90.

13. Marsh T, Pietras K, McAllister SS. Fibroblasts as architects of cancer pathogenesis. Biochim Biophys Acta 2013; 1832 (7): 1070–1078. doi: 10.1016/j.bbadis.2012.10.013.

14. Sousa AM, Liu T, Guevara O et al. Smooth muscle alpha-actin expression and myofibroblast differentiation by TGFbeta are dependent upon MK2. J Cell Biochem 2007; 100 (6): 1581–1592. doi: 10.1002/jcb.21154.

15. Muller GA, Rodemann HP. Characterization of human renal fibroblasts in health and disease: I. Immunophenotyping of cultured tubular epithelial cells and fibroblasts derived from kidneys with histologically proven interstitial fibrosis. Am J Kidney Dis 1991; 17 (6): 680–683. doi: 10.1016/s0272-6386 (12) 80351-9.

16. Huang SK, Horowitz JC. Outstaying their welcome: the persistent myofibroblast in IPF. Austin J Pulm Respir Med 2014; 1 (1): 3–13.

17. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986; 315 (26): 1650–1659. doi: 10.1056/NEJM198612253152606.

18. Lagares D, Santos A, Grasberger PE et al. Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis. Sci Transl Med 2017; 9 (420): 3765. doi: 10.1126/scitranslmed.aal3765.

19. Yeo SY, Lee KW, Shin D et al. A positive feedback loop bi-stably activates fibroblasts. Nat Commun 2018; 9 (1): 3016. doi: 10.1038/s41467-018-05274-6.

20. Varga J, Trojanowska M, Kuwana M. Pathogenesis of systemic sclerosis: recent insights of molecular and cellular mechanisms and therapeutic opportunities. J Scleroderma Relat Disord 2017; 2 (3): 137–152. doi: 10.5301/jsrd.5000249.

21. Bochet L, Lehuede C, Dauvillier S et al. Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer. Cancer Res 2013; 73 (18): 5657–5668. doi: 10.1158/0008-5472.CAN-13-0530.

22. Mori L, Bellini A, Stacey MA et al. Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow. Exp Cell Res 2005; 304 (1): 81–90. doi: 10.1016/j.yexcr.2004.11.011.

23. Jung Y, Kim JK, Shiozawa Y et al. Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis. Nat Commun 2013; 4: 1795. doi: 10.1038/ncomms2766.

24. Iwano M, Plieth D, Danoff TM et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 2002; 110 (3): 341–350. doi: 10.1172/JCI15518.

25. Mink SR, Vashistha S, Zhang W et al. Cancer-associated fibroblasts derived from EGFR-TKI-resistant tumors reverse EGFR pathway inhibition by EGFR-TKIs. Mol Cancer Res 2010; 8 (6): 809–820. doi: 10.1158/1541-7786.MCR-09-0460.

26. Zeisberg EM, Potenta S, Xie L et al. Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res 2007; 67 (21): 10123–10128. doi: 10.1158/0008-5472.CAN-07-3127.

27. Bu L, Baba H, Yoshida N et al. Biological heterogeneity and versatility of cancer-associated fibroblasts in the tumor microenvironment. Oncogene 2019; 38 (25): 4887–4901. doi: 10.1038/s41388-019-0765-y.

28. Liao Z, Tan ZW, Zhu P et al. Cancer-associated fibroblasts in tumor microenvironment – accomplices in tumor malignancy. Cell Immunol 2019; 343: 103729. doi: 10.1016/j.cellimm.2017.12.003.

29. Gascard P, Tlsty TD. Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev 2016; 30 (9): 1002–1019. doi: 10.1101/gad.279737.116.

30. Maris P, Blomme A, Palacios AP et al. Asporin is a fibroblast-derived TGF-beta1 inhibitor and a tumor suppressor associated with good prognosis in breast cancer. PLoS Med 2015; 12 (9): e1001871. doi: 10.1371/journal.pmed.1001871.

31. Vazquez-Villa F, Garcia-Ocana M, Galvan JA et al. COL11A1/ (pro) collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression. Tumour Biol 2015; 36 (4): 2213–2222. doi: 10.1007/s13277-015-3295-4.

32. Leung CS, Yeung TL, Yip KP et al. Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential. Nat Commun 2014; 5: 5092. doi: 10.1038/ncomms6092.

33. DeFilippis RA, Chang H, Dumont N et al. CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues. Cancer Discov 2012; 2 (9): 826–839. doi: 10.1158/2159-8290.CD-12-0107.

34. Olumi AF, Grossfeld GD, Hayward SW et al. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Research 1999; 59 (19): 5002–5011. doi: 10.1186/bcr138.

35. Hu M, Yao J, Carroll D K et al. Regulation of in situ to invasive breast carcinoma transition. Cancer Cell 2008; 13 (5): 394–406. doi: 10.1016/j.ccr.2008.03.007.

36. Patel AK, Vipparthi K, Thatikonda V et al. A subtype of cancer-associated fibroblasts with lower expression of alpha-smooth muscle actin suppresses stemness through BMP4 in oral carcinoma. Oncogenesis 2018; 7 (10): 78. doi: 10.1038/s41389-018-0087-x.

37. Procopio MG, Laszlo C, Al Labban D et al. Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation. Nat Cell Biol 2015; 17 (9): 1193–1204. doi: 10.1038/ncb3228.

38. Hutchenreuther J, Vincent K, Norley C et al. Activation of cancer-associated fibroblasts is required for tumor neovascularization in a murine model of melanoma. Matrix Biol 2018; 74: 52–61. doi: 10.1016/j.matbio.2018.06.003.

39. Banerjee J, Mishra R, Li X et al. A reciprocal role of prostate cancer on stromal DNA damage. Oncogene 2014; 33 (41): 4924–4931. doi: 10.1038/onc.2013.431.

40. Bhattacharyya S, Wang W, Qin W et al. TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung. JCI insight 2018; 3 (13): 98850. doi: 10.1172/jci.insight.98850.

41. Xu Y, Ma J, Zheng Q et al. MPSSS impairs the immunosuppressive function of cancer-associated fibroblasts via the TLR4-NF-κB pathway. Biosci Rep 2019; 39 (5): BSR20182171. doi: 10.1042/BSR20182171.

42. Sasaki S, Baba T, Shinagawa K et al. Crucial involvement of the CCL3-CCR5 axis-mediated fibroblast accumulation in colitis-associated carcinogenesis in mice. Int J Cancer 2014; 135 (6): 1297–1306. doi: 10.1002/ijc.28779.

43. Tanabe Y, Sasaki S, Mukaida N et al. Blockade of the chemokine receptor, CCR5, reduces the growth of orthotopically injected colon cancer cells via limiting cancer-associated fibroblast accumulation. Oncotarget 2016; 7 (30): 48335–48345. doi: 10.18632/oncotarget.10227.

44. Zhang Y, Zhang L, Lin XH et al. Knockdown of IRF3 inhibits extracellular matrix expression in keloid fibroblasts. Biomed Pharmacother 2017; 88: 1064–1068. doi: 10.1016/j.biopha.2017.01.142.

45. Zeisberg EM, Zeisberg M. The role of promoter hypermethylation in fibroblast activation and fibrogenesis. J Pathol 2013; 229 (2): 264–273. doi: 10.1002/path.4120.

46. Albrengues J, Bertero T, Grasset E et al. Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts. Nat Commun 2015; 6: 10204. doi: 10.1038/ncomms10204.

47. Alkasalias T, Moyano-Galceran L, Arsenian-Henriksson M et al. Fibroblasts in the tumor microenvironment: shield or spear? Int J Mol Sci 2018; 19 (5): 1532. doi: 10.3390/ijms19051532.

48. Alkasalias T, Flaberg E, Kashuba V et al. Inhibition of tumor cell proliferation and motility by fibroblasts is both contact and soluble factor dependent. Proc Natl Acad Sci USA 2014; 111 (48): 17188–17193. doi: 10.1073/pnas.1419554111.

49. Lee TH, Chennakrishnaiah S, Audemard E et al. Oncogenic ras-driven cancer cell vesiculation leads to emission of double-stranded DNA capable of interacting with target cells. Biochem Biophys Res Commun 2014; 451 (2): 295–301. doi: 10.1016/j.bbrc.2014.07.109.

50. Webber J, Steadman R, Mason MD et al. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res 2010; 70 (23): 9621–9630. doi: 10.1158/0008-5472.CAN-10-1722.

51. Balaj L, Lessard R, Dai L et al. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2011; 2: 180. doi: 10.1038/ncomms1180.

52. Guescini M, Genedani S, Stocchi V et al. Astrocytes and glioblastoma cells release exosomes carrying mtDNA. J Neural Transm (Vienna) 2010; 117 (1): 1–4. doi: 10.1007/s00702-009-0288-8.

53. Cai J, Han Y, Ren H et al. Extracellular vesicle-mediated transfer of donor genomic DNA to recipient cells is a novel mechanism for genetic influence between cells. J Mol Cell Biol 2013; 5 (4): 227–238. doi: 10.1093/jmcb/mjt011.

54. Waldenstrom A, Genneback N, Hellman U et al. Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells. PLoS One 2012; 7 (4): e34653. doi: 10.1371/journal.pone.0034653.

55. Orimo A, Gupta PB, Sgroi DC et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005; 121 (3): 335–348. doi: 10.1016/j.cell.2005.02.034.

56. Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov 2019; 18 (2): 99–115. doi: 10.1038/s41573-018-0004-1.

57. Seandel M, Noack-Kunnmann K, Zhu D et al. Growth factor-induced angiogenesis in vivo requires specific cleavage of fibrillar type I collagen. Blood 2001; 97 (8): 2323–2332. doi: 10.1182/blood.v97.8.2323.

58. Xing F, Saidou J, Watabe K. Cancer associated fibroblasts (CAFs) in tumor microenvironment. Front Biosci (Landmark Ed) 2010; 15: 166–179. doi: 10.2741/3613.

59. Pavlides S, Whitaker-Menezes D, Castello-Cros R et al. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009; 8 (23): 3984–4001. doi: 10.4161/cc.8.23.10 238.

60. Martinez-Outschoorn U, Sotgia F, Lisanti MP. Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function. Semin Oncol 2014; 41 (2): 195–216. doi: 10.1053/ j.seminoncol.2014.03.002.

61. Martinez-Outschoorn UE, Sotgia F Lisanti MP. Caveolae and signalling in cancer. Nat Rev Cancer 2015; 15 (4): 225–237. doi: 10.1038/nrc3915.

62. Nakajima EC, van Houten B. Metabolic symbiosis in cancer: refocusing the Warburg lens. Mol Carcinog 2013; 52 (5): 329–337. doi: 10.1002/mc.21863.

63. Kumar D, New J, Vishwakarma V et al. Cancer-associated fibroblasts drive glycolysis in a targetable signaling loop implicated in head and neck squamous cell carcinoma progression. Cancer Res 2018; 78 (14): 3769– 3782. doi: 10.1158/0008-5472.CAN-17-1076.

64. Zhang R, Qi F, Zhao F et al. Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer. Cell Death Dis 2019; 10 (4): 273. doi: 10.1038/s41419-019-1435-2.

65. Chen Q, Zhang XH, Massague J. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell 2011; 20 (4): 538–549. doi: 10.1016/j.ccr.2011.08.025.

66. Powell DW, Mifflin RC, Valentich JD et al. Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol 1999; 277 (1): C1–C9. doi: 10.1152/ajpcell.1999.277.1.C1.

67. Tse JM, Cheng G, Tyrrell JA et al. Mechanical compression drives cancer cells toward invasive phenotype. Proc Natl Acad Sci USA 2012; 109 (3): 911–916. doi: 10.1073/pnas.1118910109.

68. Karagiannis GS, Poutahidis T, Erdman SE et al. Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue. Mol Cancer Res 2012; 10 (11): 1403–1418. doi: 10.1158/1541-7786.MCR-12-0307.

69. Theveneau E, Linker C. Leaders in collective migration: are front cells really endowed with a particular set of skills? F1000Research 2017; 6: 1899. doi: 10.12688/f1000research.11889.1.

70. Erdogan B, Ao M, White L M et al. Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin. J Cell Biol 2017; 216 (11): 3799– 3816. doi: 10.1083/jcb.201704053.

71. Labernadie A, Kato T, Brugues A et al. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat Cell Biol 2017; 19 (3): 224–237. doi: 10.1038/ncb3478.

72. Li G, Satyamoorthy K, Meier F et al. Function and regulation of melanoma-stromal fibroblast interactions: when seeds meet soil. Oncogene 2003; 22 (20): 3162–3171. 10.1038/sj.onc.1206455.

73. Goetz JG, Minguet S, Navarro-Lerida I et al. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell 2011; 146 (1): 148–163. doi: 10.1016/j.cell.2011.05.040.

74. O’Connell JT, Sugimoto H, Cooke VG et al. 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. doi: 10.1073/ pnas.1109493108.

75. Calon A, Espinet E, Palomo-Ponce S et al. Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for metastasis initiation. Cancer Cell 2012; 22 (5): 571–584. doi: 10.1016/j.ccr.2012.08.013.

76. Wheeler SE, Shi H, Lin F et al. Enhancement of head and neck squamous cell carcinoma proliferation, invasion, and metastasis by tumor-associated fibroblasts in preclinical models. Head Neck 2014; 36 (3): 385–392. doi: 10.1002/hed.23312.

77. Routray S, Sunkavali A, Bari KA. Carcinoma-associated fibroblasts, its implication in head and neck squamous cell carcinoma: a mini review. Oral Dis 2014; 20 (3): 246–253. doi: 10.1111/odi.12107.

78. Barnett RM, Vilar E. Targeted therapy for cancer-associated fibroblasts: are we there yet? J Natl Cancer Inst 2017; 110 (1): 11–13. doi: 10.1093/jnci/djx131.

79. Dudas J, Fullar A, Bitsche M et al. 9 Matrix remodeling in head and neck squamous cell carcinomais. Oral Oncol 2015; 51 (5): e30. doi: 10.1016/j.oraloncology.2015.02. 012.

80. Alvarez-Teijeiro S, Garcia-Inclan C, Villaronga MA et al. Factors secreted by cancer-associated fibroblasts that sustain cancer stem properties in head and neck squamous carcinoma cells as potential therapeutic targets. Cancers 2018; 10 (9): 334. doi: 10.3390/cancers10090334.

81. Jiffar T, Yilmaz T, Lee J et al. Brain derived neutrophic factor (BDNF) coordinates lympho-vascular metastasis through a fibroblast-governed paracrine axis in the tumor microenvironment. Cancer Cell Microenviron 2017; 4 (2): 1566. doi: 10.14800/ccm.1566.

82. Kupferman ME, Jiffar T, El-Naggar A et al. TrkB induces EMT and has a key role in invasion of head and neck squamous cell carcinoma. Oncogene 2010; 29 (14): 2047–2059. doi: 10.1038/onc.2009.486.

83. Bagordakis E, Sawazaki-Calone I, Macedo CC et al. Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures. Tumour Biol 2016; 37 (7): 9045–9057. doi: 10.1007/s13277-015-4629-y.

84. Choi SY, Oh SY, Kang SH et al. NAB 2-Expressing cancer-associated fibroblast promotes HNSCC progression. Cancers 2019; 11 (3): 388. doi: 10.3390/cancers11030388.

85. Sok JC, Lee JA, Dasari S et al. Collagen type XI α1 facilitates head and neck squamous cell cancer growth and invasion. Br J Cancer 2013; 109 (12): 3049–3056. doi: 10.1038/bjc.2013.624.

86. Utispan K, Koontongkaew S. Fibroblasts and macrophages: key players in the head and neck cancer microenvironment. J Oral Biosci 2017; 59 (1): 23–30. doi: 10.1016/j.job.2016.11.002.

87. Yu B, Wu K, Wang X et al. Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7. Cell Death Dis 2018; 9 (11): 1082. doi: 10.1038/s41419-018-1116-6.

88. Kinugasa Y, Matsui T, Takakura N. CD44 expressed on cancer-associated fibroblasts is a functional molecule supporting the stemness and drug resistance of malignant cancer cells in the tumor microenvironment. Stem Cells 2014; 32 (1): 145–156. doi: 10.1002/stem.1556.

89. Alcolea S, Antón R, Camacho M et al. Interaction between head and neck squamous cell carcinoma cells and fibroblasts in the biosynthesis of PGE2. J Lipid Res 2012; 53 (4): 630–642. doi: 10.1194/jlr.M019695.

90. Cohen EG, Almahmeed T, Du B et al. Microsomal prostaglandin E synthase-1 is overexpressed in head and neck squamous cell carcinoma. Clin Cancer Res 2003; 9 (9): 3425–3430.

91. Abrahao AC, Castilho RM, Squarize CH et al. A role for COX2-derived PGE2 and PGE2-receptor subtypes in head and neck squamous carcinoma cell proliferation. Oral Oncology 2010; 46 (12): 880–887. doi: 10.1016/j.oraloncology.2010.09.005.

92. Chakravarthy A, Khan L, Bensler NP et al. TGF-β-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure. Nat Commun 2018; 9 (1): 4692. doi: 10.1038/s41467-018-06654-8.

93. Steinbichler TB, Metzler V, Pritz C et al. Tumor-associated fibroblast-conditioned medium induces CDDP resistance in HNSCC cells. Oncotarget 2016; 7 (3): 2508–2518. doi: 10.18632/oncotarget.6210.

94. New J, Arnold L, Ananth M et al. Secretory autophagy in cancer-associated fibroblasts promotes head and neck cancer progression and offers a novel therapeutic target. Cancer Res 2017; 77 (23): 6679–6691. doi: 10.1158/0008-5472.CAN-17-1077.

95. Gandhi MK, Moll G, Smith C et al. Galectin-1 mediated suppression of Epstein-Barr virus specific T-cell immunity in classic Hodgkin lymphoma. Blood 2007; 110 (4): 1326–1329. doi: 10.1182/blood-2007-01-066100.

96. Munoz-Suano A, Hamilton AB, Betz AG. Gimme shelter: the immune system during pregnancy. Immunol Rev 2011; 241 (1): 20–38. doi: 10.1111/j.1600-065X.2011.01002.x.

97. Wu MH, Hong HC, Hong TM et al. Targeting galectin-1 in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis by downregulating MCP-1/CCL2 expression. Clin Cancer Res 2011; 17 (6): 1306–1316. doi: 10.1158/1078-0432.CCR-10-1824.

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