TGF-β1 诱导的基质 POSTN 促进卵巢癌细胞的迁移和侵袭。

Stromal POSTN induced by TGF-β1 facilitates the migration and invasion of ovarian cancer.

机构信息

Obstetrics and Gynecology Hospital, Fudan University, No.419, Fangxie Road, Shanghai 200011, China.; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.

Obstetrics and Gynecology Hospital, Fudan University, No.419, Fangxie Road, Shanghai 200011, China.; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China..

出版信息

Gynecol Oncol. 2021 Feb;160(2):530-538. doi: 10.1016/j.ygyno.2020.11.026. Epub 2020 Dec 13.

DOI:10.1016/j.ygyno.2020.11.026

PMID:33317907

Abstract

OBJECTIVE

Periostin (POSTN) overexpression observed in various cancer types is correlated with metastasis and tumor progression. However, its effect on the crosstalk between ovarian cancer cells and cancer-associated fibroblasts (CAFs) remains elusive. This study aims to ascertain the role of CAF-derived POSTN in the ovarian cancer microenvironment.

METHODS

POSTN expression in high-grade serous ovarian cancer (HGSC) was detected through immunochemistry. Transwell assay was conducted to determine cell migration and invasion. POSTN was knocked down or overexpressed using lentiviral vectors. The potential downstream effects of POSTN were explored and verified by RNA sequencing and western blotting, respectively. In vitro metastatic capability of ovarian cancer cells regulated by POSTN was determined by indirect co-culture.

RESULTS

POSTN was highly enriched in HGSC stromal components, particularly in fibroblasts, while its overexpression was correlated with reduced overall survival (OS). CAF-derived POSTN functioned as a ligand for integrin αvβ3, fueling the migration and invasion of ovarian cancer cells by activating the PI3K/Akt pathway and inducing the epithelial-mesenchymal transition (EMT). Additionally, the pro-metastatic properties and the activation of fibroblasts induced by TGF-β1 partly relied on POSTN.

CONCLUSIONS

Stromal-derived POSTN drives the remodeling of the pro-metastatic microenvironment, which might be as a potential therapeutic target in patients with ovarian cancer.

摘要

目的

在多种癌症类型中观察到的骨桥蛋白（POSTN）过表达与转移和肿瘤进展相关。然而，其对卵巢癌细胞与癌相关成纤维细胞（CAF）之间串扰的影响仍不清楚。本研究旨在确定 CAF 来源的 POSTN 在卵巢癌微环境中的作用。

方法

通过免疫化学检测高级别浆液性卵巢癌（HGSC）中 POSTN 的表达。通过 Transwell 测定进行细胞迁移和侵袭实验。使用慢病毒载体敲低或过表达 POSTN。通过 RNA 测序和 Western blot 分别探索和验证 POSTN 的潜在下游效应。通过间接共培养来确定 POSTN 调节的卵巢癌细胞的体外转移能力。

结果

POSTN 在 HGSC 基质成分中高度富集，特别是在成纤维细胞中，而过表达与总生存期（OS）降低相关。CAF 来源的 POSTN 作为整合素αvβ3 的配体发挥作用，通过激活 PI3K/Akt 通路并诱导上皮-间充质转化（EMT），促进卵巢癌细胞的迁移和侵袭。此外，TGF-β1 诱导的促转移特性和成纤维细胞的激活部分依赖于 POSTN。