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

Phuong T. Huynh, Ellen J. Beswick, Yun A. Coronado, Paul Johnson, Malaney R. O'Connell, Tammara Watts, Pomila Singh, Suimin Qiu, Katherine Morris, Don W. Powell, Iryna Pinchuk

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1971-1981
Number of pages11
JournalInternational Journal of Cancer
Volume138
Issue number8
DOIs
StatePublished - Apr 15 2016

Fingerprint

Neoplastic Stem Cells
Stromal Cells
Colorectal Neoplasms
Interleukin-6
Inflammation
Neoplasms
Myofibroblasts
Th17 Cells
Fibroblasts
Aldehyde Dehydrogenase
Caco-2 Cells
Adaptive Immunity
Conditioned Culture Medium
Growth
Coculture Techniques
Colonic Neoplasms
Colon
Mucous Membrane
Stem Cells
Cytokines

Keywords

  • CD90+ fibroblasts
  • colorectal cancer
  • IL-6
  • inflammation
  • tumor stem cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Huynh, P. T., Beswick, E. J., Coronado, Y. A., Johnson, P., O'Connell, M. R., Watts, T., ... Pinchuk, I. (2016). CD90+ stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer. International Journal of Cancer, 138(8), 1971-1981. https://doi.org/10.1002/ijc.29939

CD90+ stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer. / Huynh, Phuong T.; Beswick, Ellen J.; Coronado, Yun A.; Johnson, Paul; O'Connell, Malaney R.; Watts, Tammara; Singh, Pomila; Qiu, Suimin; Morris, Katherine; Powell, Don W.; Pinchuk, Iryna.

In: International Journal of Cancer, Vol. 138, No. 8, 15.04.2016, p. 1971-1981.

Research output: Contribution to journalArticle

Huynh, PT, Beswick, EJ, Coronado, YA, Johnson, P, O'Connell, MR, Watts, T, Singh, P, Qiu, S, Morris, K, Powell, DW & Pinchuk, I 2016, 'CD90+ stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer', International Journal of Cancer, vol. 138, no. 8, pp. 1971-1981. https://doi.org/10.1002/ijc.29939
Huynh, Phuong T. ; Beswick, Ellen J. ; Coronado, Yun A. ; Johnson, Paul ; O'Connell, Malaney R. ; Watts, Tammara ; Singh, Pomila ; Qiu, Suimin ; Morris, Katherine ; Powell, Don W. ; Pinchuk, Iryna. / CD90+ stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer. In: International Journal of Cancer. 2016 ; Vol. 138, No. 8. pp. 1971-1981.
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