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10.1002/ijc.29939

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suck abstract from ncbi


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pmid26595254      Int+J+Cancer 2016 ; 138 (8): 1971-81
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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 #MMPMID26595254
  • Huynh PT; Beswick EJ; Coronado YA; Johnson P; O'Connell MR; Watts T; Singh P; Qiu S; Morris K; Powell DW; Pinchuk IV
  • Int J Cancer 2016[Apr]; 138 (8): 1971-81 PMID26595254show ga
  • 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 co-culture 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. Expression of stem cell markers-aldehyde dehydrogenase (ALDH) 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 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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