Gynecologic oncology · 2020
Stromal POSTN induced by TGF-β1 facilitates the migration and invasion of ovarian cancer.
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Yue Huiran, Li Wenzhi, Chen Ruifang, Wang Jieyu, Lu Xin, Li Jun
Аннотация
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.
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.
Предметные рубрики MeSH
Biomarkers, TumorCancer-Associated FibroblastsCarcinoma, Ovarian EpithelialCell Adhesion MoleculesCell Line, TumorCell ProliferationCoculture TechniquesDatasets as TopicEpithelial-Mesenchymal TransitionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansNeoplasm InvasivenessOvarian NeoplasmsPhosphatidylinositol 3-KinasesPrognosisProto-Oncogene Proteins c-aktSignal TransductionTransforming Growth Factor beta1Tumor MicroenvironmentUp-Regulation