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| 標題: | COL11A1 activates cancer-associated fibroblasts by modulating TGF-beta 3 through the NF-kappa B/IGFBP2 axis in ovarian cancer cells |
| 作者: | Wu, Yi-Hui
Huang, Yu-Fang
Chang, Tzu-Hao
Chen, Chien-Chin
Wu, Pei-Ying
Huang, Soon-Cen
Chou, Cheng-Yang |
| 貢獻者: | Chi Mei Med Ctr, Dept Med Res
Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Obstet & Gynecol
Taipei Med Univ, Grad Inst Biomed Informat
Chia Yi Christian Hosp, Dept Pathol, Ditmanson Med Fdn
Chia Nan Univ Pharm & Sci, Dept Cosmet Sci
Chi Mei Med Ctr, Dept Obstet & Gynecol |
| 關鍵字: | NF-KAPPA-B
TGF-BETA
BREAST-CANCER
CARCINOMA
GROWTH
EXPRESSION
IL-6
CHEMORESISTANCE
SIGNATURE
SURVIVAL |
| 日期: | 2021 |
| 上傳時間: | 2023-11-11 11:50:23 (UTC+8) |
| 出版者: | SPRINGERNATURE |
| 摘要: | Ovarian cancer has a unique tumor microenvironment (TME) that enables cancer-associated fibroblasts (CAFs) to interact with cellular and matrix constituents and influence tumor development and migration into the peritoneal cavity. Collagen type XI alpha 1 (COL11A1) is overexpressed in CAFs; therefore this study examines its role during CAF activation in epithelial ovarian cancer (EOC). Coculturing human ovarian fibroblasts (HOFs) with high COL11A1-expressing EOC cells or exposure to the conditioned medium of these cells prompted the expression of COL11A1 and CAF phenotypes. Conversely, coculturing HOFs with low COL11A1-expressing EOC cells or COL11A1-knockdown abrogated COL11A1 overexpression and secretion, in addition to CAF activation. Increased p-SP1 expression attributed to COL11A1-mediated extracellular signal-regulated kinase activation (ERK) induced p65 translocation into the nucleus and augmented its binding to the insulin-like growth factor binding protein 2 (IGFBP2) promoter, ultimately inducing TGF-beta 3 activation. The CAF-cancer cell crosstalk triggered interleukin-6 release, which in turn promoted EOC cell proliferation and invasiveness. These in vitro results were confirmed by in vivo findings in a mouse model, showing that COL11A1 overexpression in EOC cells promoted tumor formation and CAF activation, which was inhibited by TGF-beta 3 antibody. Human tumors with high TGF-beta 3 levels showed elevated expression of COL11A1 and IGFBP2, which was associated with poor survival. Our findings suggest the possibility that anti-TGF-beta 3 treatment strategy may be effective in targeting CAFs in COL11A1-positive ovarian tumors. |
| 關聯: | ONCOGENE, v.40, n.26, pp.4503-4519 |
| 顯示於類別: | [化妝品應用與管理系(所)] 期刊論文
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