Cancer Associated Fibroblasts and Its Role in The Evolution of Gastrointestinal Neoplasms_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 SONGShu-zheng ,  YUJi-wei

The First Department of General Surgery, Third People's Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 201999, China;

Corresponding author：

YUJi-wei, Email: jiweiyu919@hotmail.com

Keywords：

Cancer associated fibroblasts; Tumor microenvironment; Gastrointestinal neoplasm

DOI：

10.7507/1007-9424.20140315

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review cancer associated fibroblasts(CAFs) and its role in the evolution of gastrointestinal neoplasms. Method Domestic and international publications in relation to CAFs and its role in the evolution of gastrointestinal neoplasms were collected and reviewed. Results In the gastrointestinal cancers, as the largest number and the most important stromal cells of the tumor microenvironment, CAFs induce the homeostasis of cell microenviron-ment out of balance, promote the remodeling of the tumor metabolism and extracellular matrix(ECM), and thus impulse the generation, proliferation, invasion and metastasis of the tumor by secreting different kinds of cytokines. Conclusions The key role CAFs playing in the tumor generation and evolution makes themselves and the multiple relatively specific molecules they secrete a new target for prognosis and targeted therapy, and this gives us a new idea for the combined treatment of gastrointestinal tumor or any other tumors.

Citation： SONGShu-zheng, YUJi-wei. Cancer Associated Fibroblasts and Its Role in The Evolution of Gastrointestinal Neoplasms. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(10): 1311-1315. doi: 10.7507/1007-9424.20140315 Copy

1.	Tripathi M, Billet S, Bhowmick NA.Understanding the role of stromal fibroblasts in cancer progression[J]. Cell Adh Migr, 2012, 6(3):231-235.
2.	Olumi AF, Grossfeld GD, Hayward SW, et al.Carcinoma-asso-ciated fibroblasts direct tumor progression of initiated human prostatic epithelium[J]. Cancer Res, 1999, 59(19):5002-5011.
3.	Orimo A, Weinberg RA.Stromal fibroblasts in cancer:a novel tumor-promoting cell type[J]. Cell Cycle, 2006, 5(15):1597-1601.
4.	Orimo A, Weinberg RA.Heterogeneity of stromal fibroblasts in tumor[J]. Cancer Biol Ther, 2007, 6(4):618-619.
5.	Jiang L, Gonda TA, Gamble MV, et al.Global hypomethylation of genomic DNA in cancer-associated myofibroblasts[J]. Cancer Res, 2008, 68(23):9900-9908.
6.	De Wever O, Demetter P, Mareel M, et al.Stromal myofibroblasts are drivers of invasive cancer growth[J]. Int J Cancer, 2008, 123(10):2229-2238.
7.	De Boeck A, Narine K, De Neve W, et al.Resident and bone marrow-derived mesenchymal stem cells in head and neck squamous cell carcinoma[J]. Oral Oncol, 2010, 46(5):336-342.
8.	Gu J, Qian H, Shen L, et al.Gastric cancer exosomes trigger differentiation of umbilical cord derived mesenchymal stem cells to carcinoma-associated fibroblasts through TGF-β/Smad pathway[J]. PloS one, 2012, 7(12):e52465.
9.	De Boeck A, Hendrix A, Maynard D, et al.Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression[J]. Proteomics, 2013, 13(2):379-388.
10.	Gonda TA, Tu S, Wang TC.Chronic inflammation, the tumor microenvironment and carcinogenesis[J]. Cell Cycle, 2009, 8(13):2005-2013.
11.	Kanzawa M, Semba S, Hara S, et al.WNT5A is a key regulator of the epithelial-mesenchymal transition and cancer stem cell properties in human gastric carcinoma cells[J]. Pathobiology, 2013, 80(5):235-244.
12.	Thiery JP, Acloque H, Huang RY, et al.Epithelial-mesenchymal transitions in development and disease[J]. Cell, 2009, 139(5):871-890.
13.	Fuyuhiro Y, Yashiro M, Noda S, et al.Upregulation of cancer-associated myofibroblasts by TGF-βfrom scirrhous gastric carcinoma cells[J]. Br J Cancer, 2011, 105(7):996-1001.
14.	Wu X, Chen X, Zhou Q, et al.Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer[J]. Cancer Lett, 2013, 335(1):128-135.
15.	Finger EC, Giaccia AJ.Hypoxia, inflammation, and the tumor microenvironment in metastatic disease[J]. Cancer Metastasis Rev, 2010, 29(2):285-293.
16.	Straus DS.TNFalpha and IL-17 cooperatively stimulate glucose metabolism and growth factor production in human colorectal cancer cells[J]. Mol cancer, 2013, 12(78):1476-4598.
17.	Scheel C, Eaton EN, Li SH, et al.Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast[J]. Cell, 2011, 145(6):926-940.
18.	Kalluri R, Zeisberg M.Fibroblasts in cancer[J]. Nat Rev Cancer, 2006, 6(5):392-401.
19.	Pena C, Cespedes MV, Lindh MB, et al.STC1 expression by cancer-associated fibroblasts drives metastasis of colorectal cancer[J]. Cancer Res, 2013, 73(4):1287-1297.
20.	Zhu Y, Zhu M, Lance P.Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells[J]. Biochem Biophys Res Commun, 2012, 425(3):607-612.
21.	Mao Q, Zhang Y, Fu X, et al.A tumor hypoxic niche protects human colon cancer stem cells from chemotherapy[J]. J Cancer Res Clin Oncol, 2013, 139(2):211-222.
22.	Cirri P, Chiarugi P.Cancer-associated-fibroblasts and tumour cells:a diabolic liaison driving cancer progression[J]. Cancer Metastasis Rev, 2012, 31(1-2):195-208.
23.	Glaire MA, El-Omar EM, Wang TC, et al.The mesenchyme in malignancy:a partner in the initiation, progression and dissemination of cancer[J]. Pharmacol Ther, 2012, 136(2):131-141.
24.	Powell D, Pinchuk I, Saada J, et al. Mesenchymal cells of the intestinal lamina propria[J]. Annu Rev Physiol, 2011, 73:213-237.
25.	Aggarwal S, Brennen WN, Kole TP, et al.Fibroblast activation protein peptide substrates identified from human collagen I derived gelatin cleavage sites[J]. Biochemistry, 2008, 47(3):1076-1086.
26.	Sung CO, Lee KW, Han S, et al.Twist1 is up-regulated in gastric cancer-associated fibroblasts with poor clinical outcomes[J]. Am J Pathol, 2011, 179(4):1827-1838.
27.	Yoshio T, Morita T, Kimura Y, et al.Caldesmon suppresses cancer cell invasion by regulating podosome/invadopodium formation[J]. FEBS Letters, 2007, 581(20):3777-3782.
28.	Kohler C.Histochemical localization of caldesmon isoforms in colon adenocarcinoma and lymph node metastases[J]. Virchows Arch, 2011, 459(1):81-89.
29.	Karagiannis GS, Petraki C, Prassas I, et al.Proteomic signatures of the desmoplastic invasion front reveal collagen typeⅫas a marker of myofibroblastic differentiation during colorectal cancer metastasis[J]. Oncotarget, 2012, 3(3):267-285.
30.	Yashiro M, Hirakawa K.Cancer-stromal interactions in scirrhous gastric carcinoma[J]. Cancer Microenviron, 2010, 3(1):127-135.
31.	Zhu Y, Zhu M, Lance P.IL1beta-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithe-lial cancer cells[J]. Exp Cell Res, 2012, 318(19):2520-2530.
32.	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[J]. Cancer Cell, 2012, 22(5):571-584.
33.	Zhi K, Shen X, Zhang H, et al.Cancer-associated fibroblasts are positively correlated with metastatic potential of human gastric cancers[J]. J Exp Clin Res, 2010, 29(66):1756-1766.
34.	Zhuang Z, Zhou R, Xu X, et al.Clinical significance of integrin alphavbeta6 expression effects on gastric carcinoma invasiveness and progression via cancer-associated fibroblasts[J]. Med Oncol, 2013, 30(3):580.
35.	Herrera M, Herrera A, Dominguez G, et al.Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients[J]. Cancer Sci, 2013, 104(4):437-444.
36.	Saigusa S, Toiyama Y, Tanaka K, et al.Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy[J]. Int J Oncol, 2011, 38(3):655-663.
37.	de la Peña S, Sampieri CL, Leon-Cordoba K.Matrix metalloproteases as molecular markers in gastric cancer[J]. Med Clin (Barc), 2010, 134(3):123-126.
38.	Hasegawa T, Yashiro M, Nishii T, et al.Cancer-associated fibroblasts might sustain the stemness of scirrhous gastric cancer cells via transforming growth factor-beta signaling[J]. Int J Cancer, 2014, 134(8):1785-1795.
39.	Akishima-Fukasawa Y, Ino Y, Nakanishi Y, et al.Significance of PGP9.5 expression in cancer-associated fibroblasts for prognosis of colorectal carcinoma[J]. Am J Clin Pathol, 2010, 134(1):71-79.
40.	Yamanashi T, Nakanishi Y, Fujii G, et al.Podoplanin expression identified in stromal fibroblasts as a favorable prognostic marker in patients with colorectal carcinoma[J]. Oncology, 2009, 77(1):53-62.
41.	Sotgia F, Martinez-Outschoorn UE, Howell A, et al.Caveolin-1 and cancer metabolism in the tumor microenvironment:markers, models, and mechanisms[J]. Annu Rev Pathol, 2012, 7:423-467.
42.	Zhao X, He Y, Gao J, et al.Caveolin-1 expression level in cancer associated fibroblasts predicts outcome in gastric cancer[J]. PLoS One, 2013, 8(3):e59102.
43.	Santos AM, Jung J, Aziz N, et al.Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice[J]. J Clin Invest, 2009, 119(12):3613-3625.

1. Tripathi M, Billet S, Bhowmick NA.Understanding the role of stromal fibroblasts in cancer progression[J]. Cell Adh Migr, 2012, 6(3):231-235.
2. Olumi AF, Grossfeld GD, Hayward SW, et al.Carcinoma-asso-ciated fibroblasts direct tumor progression of initiated human prostatic epithelium[J]. Cancer Res, 1999, 59(19):5002-5011.
3. Orimo A, Weinberg RA.Stromal fibroblasts in cancer:a novel tumor-promoting cell type[J]. Cell Cycle, 2006, 5(15):1597-1601.
4. Orimo A, Weinberg RA.Heterogeneity of stromal fibroblasts in tumor[J]. Cancer Biol Ther, 2007, 6(4):618-619.
5. Jiang L, Gonda TA, Gamble MV, et al.Global hypomethylation of genomic DNA in cancer-associated myofibroblasts[J]. Cancer Res, 2008, 68(23):9900-9908.
6. De Wever O, Demetter P, Mareel M, et al.Stromal myofibroblasts are drivers of invasive cancer growth[J]. Int J Cancer, 2008, 123(10):2229-2238.
7. De Boeck A, Narine K, De Neve W, et al.Resident and bone marrow-derived mesenchymal stem cells in head and neck squamous cell carcinoma[J]. Oral Oncol, 2010, 46(5):336-342.
8. Gu J, Qian H, Shen L, et al.Gastric cancer exosomes trigger differentiation of umbilical cord derived mesenchymal stem cells to carcinoma-associated fibroblasts through TGF-β/Smad pathway[J]. PloS one, 2012, 7(12):e52465.
9. De Boeck A, Hendrix A, Maynard D, et al.Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression[J]. Proteomics, 2013, 13(2):379-388.
10. Gonda TA, Tu S, Wang TC.Chronic inflammation, the tumor microenvironment and carcinogenesis[J]. Cell Cycle, 2009, 8(13):2005-2013.
11. Kanzawa M, Semba S, Hara S, et al.WNT5A is a key regulator of the epithelial-mesenchymal transition and cancer stem cell properties in human gastric carcinoma cells[J]. Pathobiology, 2013, 80(5):235-244.
12. Thiery JP, Acloque H, Huang RY, et al.Epithelial-mesenchymal transitions in development and disease[J]. Cell, 2009, 139(5):871-890.
13. Fuyuhiro Y, Yashiro M, Noda S, et al.Upregulation of cancer-associated myofibroblasts by TGF-βfrom scirrhous gastric carcinoma cells[J]. Br J Cancer, 2011, 105(7):996-1001.
14. Wu X, Chen X, Zhou Q, et al.Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer[J]. Cancer Lett, 2013, 335(1):128-135.
15. Finger EC, Giaccia AJ.Hypoxia, inflammation, and the tumor microenvironment in metastatic disease[J]. Cancer Metastasis Rev, 2010, 29(2):285-293.
16. Straus DS.TNFalpha and IL-17 cooperatively stimulate glucose metabolism and growth factor production in human colorectal cancer cells[J]. Mol cancer, 2013, 12(78):1476-4598.
17. Scheel C, Eaton EN, Li SH, et al.Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast[J]. Cell, 2011, 145(6):926-940.
18. Kalluri R, Zeisberg M.Fibroblasts in cancer[J]. Nat Rev Cancer, 2006, 6(5):392-401.
19. Pena C, Cespedes MV, Lindh MB, et al.STC1 expression by cancer-associated fibroblasts drives metastasis of colorectal cancer[J]. Cancer Res, 2013, 73(4):1287-1297.
20. Zhu Y, Zhu M, Lance P.Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells[J]. Biochem Biophys Res Commun, 2012, 425(3):607-612.
21. Mao Q, Zhang Y, Fu X, et al.A tumor hypoxic niche protects human colon cancer stem cells from chemotherapy[J]. J Cancer Res Clin Oncol, 2013, 139(2):211-222.
22. Cirri P, Chiarugi P.Cancer-associated-fibroblasts and tumour cells:a diabolic liaison driving cancer progression[J]. Cancer Metastasis Rev, 2012, 31(1-2):195-208.
23. Glaire MA, El-Omar EM, Wang TC, et al.The mesenchyme in malignancy:a partner in the initiation, progression and dissemination of cancer[J]. Pharmacol Ther, 2012, 136(2):131-141.
24. Powell D, Pinchuk I, Saada J, et al. Mesenchymal cells of the intestinal lamina propria[J]. Annu Rev Physiol, 2011, 73:213-237.
25. Aggarwal S, Brennen WN, Kole TP, et al.Fibroblast activation protein peptide substrates identified from human collagen I derived gelatin cleavage sites[J]. Biochemistry, 2008, 47(3):1076-1086.
26. Sung CO, Lee KW, Han S, et al.Twist1 is up-regulated in gastric cancer-associated fibroblasts with poor clinical outcomes[J]. Am J Pathol, 2011, 179(4):1827-1838.
27. Yoshio T, Morita T, Kimura Y, et al.Caldesmon suppresses cancer cell invasion by regulating podosome/invadopodium formation[J]. FEBS Letters, 2007, 581(20):3777-3782.
28. Kohler C.Histochemical localization of caldesmon isoforms in colon adenocarcinoma and lymph node metastases[J]. Virchows Arch, 2011, 459(1):81-89.
29. Karagiannis GS, Petraki C, Prassas I, et al.Proteomic signatures of the desmoplastic invasion front reveal collagen typeⅫas a marker of myofibroblastic differentiation during colorectal cancer metastasis[J]. Oncotarget, 2012, 3(3):267-285.
30. Yashiro M, Hirakawa K.Cancer-stromal interactions in scirrhous gastric carcinoma[J]. Cancer Microenviron, 2010, 3(1):127-135.
31. Zhu Y, Zhu M, Lance P.IL1beta-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithe-lial cancer cells[J]. Exp Cell Res, 2012, 318(19):2520-2530.
32. 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[J]. Cancer Cell, 2012, 22(5):571-584.
33. Zhi K, Shen X, Zhang H, et al.Cancer-associated fibroblasts are positively correlated with metastatic potential of human gastric cancers[J]. J Exp Clin Res, 2010, 29(66):1756-1766.
34. Zhuang Z, Zhou R, Xu X, et al.Clinical significance of integrin alphavbeta6 expression effects on gastric carcinoma invasiveness and progression via cancer-associated fibroblasts[J]. Med Oncol, 2013, 30(3):580.
35. Herrera M, Herrera A, Dominguez G, et al.Cancer-associated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients[J]. Cancer Sci, 2013, 104(4):437-444.
36. Saigusa S, Toiyama Y, Tanaka K, et al.Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy[J]. Int J Oncol, 2011, 38(3):655-663.
37. de la Peña S, Sampieri CL, Leon-Cordoba K.Matrix metalloproteases as molecular markers in gastric cancer[J]. Med Clin (Barc), 2010, 134(3):123-126.
38. Hasegawa T, Yashiro M, Nishii T, et al.Cancer-associated fibroblasts might sustain the stemness of scirrhous gastric cancer cells via transforming growth factor-beta signaling[J]. Int J Cancer, 2014, 134(8):1785-1795.
39. Akishima-Fukasawa Y, Ino Y, Nakanishi Y, et al.Significance of PGP9.5 expression in cancer-associated fibroblasts for prognosis of colorectal carcinoma[J]. Am J Clin Pathol, 2010, 134(1):71-79.
40. Yamanashi T, Nakanishi Y, Fujii G, et al.Podoplanin expression identified in stromal fibroblasts as a favorable prognostic marker in patients with colorectal carcinoma[J]. Oncology, 2009, 77(1):53-62.
41. Sotgia F, Martinez-Outschoorn UE, Howell A, et al.Caveolin-1 and cancer metabolism in the tumor microenvironment:markers, models, and mechanisms[J]. Annu Rev Pathol, 2012, 7:423-467.
42. Zhao X, He Y, Gao J, et al.Caveolin-1 expression level in cancer associated fibroblasts predicts outcome in gastric cancer[J]. PLoS One, 2013, 8(3):e59102.
43. Santos AM, Jung J, Aziz N, et al.Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice[J]. J Clin Invest, 2009, 119(12):3613-3625.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Cancer Associated Fibroblasts and Its Role in The Evolution of Gastrointestinal Neoplasms

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