論文 - 詳細
| RRC ID | 32633 |
|---|---|
| 著者 | Nagura M, Matsumura N, Baba T, Murakami R, Kharma B, Hamanishi J, Yamaguchi K, Abiko K, Koshiyama M, Mandai M, Murata T, Murphy SK, Konishi I. |
| タイトル | Invasion of uterine cervical squamous cell carcinoma cells is facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta. |
| ジャーナル | Gynecol Oncol |
| Abstract |
OBJECTIVE:Local invasion is a common pattern of spread in uterine cervical squamous cell carcinoma (CSCC). Although transforming growth factor-beta (TGF-β) facilitates invasion of various types of cancer cells, the role of the TGF-β pathway in CSCC is unclear. In this study, we analyzed the role of TGF-β signaling in the progression of CSCC. METHODS:Immunohistochemistry was used to examine the expression of TGF-β pathway molecules in 67 CSCC samples with clinicopathological data. Activation of the TGF-β pathway was investigated following co-culture of CSCC cells and cervical cancer-associated fibroblasts (CCAFs). RESULTS:Clinicopathological analysis of CSCC samples revealed that prominent expression of TGF-β receptor-2 was more frequent in CSCC with lymphovascular space invasion (LVSI) than without LVSI (p < 0.01). Lymph node metastasis was more frequent in cases in which phosphorylated SMAD3 (pSMAD3) was localized exclusively at the boundary of tumor clusters (n = 9, p < 0.05). Recombinant TGF-β1 increased pSMAD3 expression and enhanced cellular invasion (p < 0.005) in CSCC cells, which was attenuated by an inhibitor of the TGF-β receptor (p < 0.005). Enhanced pSMAD3 expression and invasion was also observed when conditioned media from CSCC cells co-cultured with CCAFs were administered. Luciferase assays showed that this medium contained a large amount of active TGF-β. Along with TGF-β activation, thrombospondin-1 was upregulated in both CSCC cells and CCAFs, while thrombospondin-1 silencing in either CSCC cells or CCAFs repressed the activity of TGF-β. Thrombospondin-1 was prominently expressed in cases with pSMAD3 boundary staining (p < 0.05). CONCLUSIONS:These results suggest that interaction between CSCC cells and surrounding CCAFs activates TGF-β via thrombospondin-1 secretion to facilitate CSCC invasion. |
| 巻・号 | 136(1) |
| ページ | 104-11 |
| 公開日 | 2015-1-1 |
| DOI | 10.1016/j.ygyno.2014.11.075 |
| PII | S0090-8258(14)01548-0 |
| PMID | 25434636 |
| MeSH | Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Communication / physiology* Female Fibroblasts / metabolism Fibroblasts / pathology* Humans Middle Aged Neoplasm Invasiveness Neoplasm Staging Signal Transduction Transforming Growth Factor beta / metabolism* Uterine Cervical Neoplasms / metabolism Uterine Cervical Neoplasms / pathology* |
| IF | 4.623 |
| 引用数 | 10 |
| リソース情報 | |
| ヒト・動物細胞 | Ca Ski(RCB1947) ME-180(RCB2106) QG-U(RCB0688) SKG-IIIa(RCB1892) |