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CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer.

Publication ,  Journal Article
Huynh, PT; Beswick, EJ; Coronado, YA; Johnson, P; O'Connell, MR; Watts, T; Singh, P; Qiu, S; Morris, K; Powell, DW; Pinchuk, IV
Published in: Int J Cancer
April 15, 2016

IL-6 is a pleiotropic cytokine increased in CRC and known to directly promote tumor growth. Colonic myofibroblasts/fibroblasts (CMFs or stromal cells) are CD90(+) innate immune cells representing up to 30% of normal colonic mucosal lamina propria cells. They are expanded in CRC tumor stroma, where they also known as a cancer associated fibroblasts (CAFs). Cells of mesenchymal origin, such as normal myofibroblasts/fibroblasts, are known to secrete IL-6; however, their contribution to the increase in IL-6 in CRC and to tumor-promoting inflammation is not well defined. Using in situ, ex vivo and coculture analyses we have demonstrated that the number of IL-6 producing CMFs is increased in CRC (C-CMFs) and they represent the major source of IL-6 in T2-T3 CRC tumors. Activity/expression of stem cell markers-aldehyde dehydrogenase and LGR5- was significantly up-regulated in colon cancer cells (SW480, Caco-2 or HT29) cultured in the presence of conditioned medium from tumor isolated C-CMFs in an IL-6 dependent manner. C-CMF and its derived condition medium, but not normal CMF isolated from syngeneic normal colons, induced differentiation of tumor promoting inflammatory T helper 17 cells (Th17) cell responses in an IL-6 dependent manner. Our study suggests that CD90(+) fibroblasts/myofibroblasts may be the major source of IL-6 in T2-T3 CRC tumors, which supports the stemness of tumor cells and induces an immune adaptive inflammatory response (a.k.a. Th17) favoring tumor growth. Taken together our data supports the notion that IL-6 producing CAFs (a.k.a. C-CMFs) may provide a useful target for treating or preventing CRCs.

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

April 15, 2016

Volume

138

Issue

8

Start / End Page

1971 / 1981

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Thy-1 Antigens
  • T-Lymphocytes
  • Stromal Cells
  • Real-Time Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Microscopy, Confocal
  • Interleukin-6
  • Inflammation
 

Citation

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Huynh, P. T., Beswick, E. J., Coronado, Y. A., Johnson, P., O’Connell, M. R., Watts, T., … Pinchuk, I. V. (2016). CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer. Int J Cancer, 138(8), 1971–1981. https://doi.org/10.1002/ijc.29939
Huynh, Phuong T., Ellen J. Beswick, Yun A. Coronado, Paul Johnson, Malaney R. O’Connell, Tammara Watts, Pomila Singh, et al. “CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer.Int J Cancer 138, no. 8 (April 15, 2016): 1971–81. https://doi.org/10.1002/ijc.29939.
Huynh PT, Beswick EJ, Coronado YA, Johnson P, O’Connell MR, Watts T, et al. CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer. Int J Cancer. 2016 Apr 15;138(8):1971–81.
Huynh, Phuong T., et al. “CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer.Int J Cancer, vol. 138, no. 8, Apr. 2016, pp. 1971–81. Pubmed, doi:10.1002/ijc.29939.
Huynh PT, Beswick EJ, Coronado YA, Johnson P, O’Connell MR, Watts T, Singh P, Qiu S, Morris K, Powell DW, Pinchuk IV. CD90(+) stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer. Int J Cancer. 2016 Apr 15;138(8):1971–1981.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

April 15, 2016

Volume

138

Issue

8

Start / End Page

1971 / 1981

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Thy-1 Antigens
  • T-Lymphocytes
  • Stromal Cells
  • Real-Time Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Microscopy, Confocal
  • Interleukin-6
  • Inflammation