論文 - 詳細
| RRC ID | 73378 |
|---|---|
| 著者 | Rattanasinchai C, Navasumrit P, Ruchirawat M. |
| タイトル | Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma. |
| ジャーナル | Sci Rep |
| Abstract |
Intrahepatic cholangiocarcinoma (iCCA) arises along the peripheral bile ducts and is often accompanied by a tumor microenvironment (TME) high in extracellular matrices (ECMs). In this study, we aimed to evaluate whether an ECM-rich TME favors iCCA progression. We identified ITGA2, which encodes collagen-binding integrin α2, to be differentially-expressed in iCCA tumors compared with adjacent normal tissues. Elevated ITGA2 is also positively-correlated with its ligand, collagen type I. Increased ITGA2 expression and its role in collagen type I binding was validated in vitro using four iCCA cell lines, compared with a non-cancerous, cholangiocyte cell line. Robust interaction of iCCA cells with collagen type I was abolished by either ITGA2 depletion or integrin α2β1-selective inhibitor treatment. In a phenotypic study, collagen type I significantly enhances clonogenic growth of HuCCA-1 and HuCCT-1 cells by three and sixfold, respectively. Inhibition of integrin α2 expression or its activity significantly blocks collagen type I-induced colony growth in both cell lines. Taken together, our data provide mechanistic evidence that collagen type I promotes growth of iCCA colonies through integrin α2 suggesting that the collagen type I-integrin α2 axis could be a promising target for cancer prevention and a therapeutic opportunity for this cancer. |
| 巻・号 | 12(1) |
| ページ | 22429 |
| 公開日 | 2022-12-27 |
| DOI | 10.1038/s41598-022-26747-1 |
| PII | 10.1038/s41598-022-26747-1 |
| PMID | 36575207 |
| PMC | PMC9794692 |
| MeSH | Bile Duct Neoplasms* / genetics Bile Duct Neoplasms* / pathology Bile Ducts, Intrahepatic / pathology Cholangiocarcinoma* / genetics Cholangiocarcinoma* / pathology Collagen Type I / genetics Humans Integrin alpha2 / genetics Tumor Microenvironment |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | HuCCT1(RCB1960) |