Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 85 Wujin Road, Shanghai, 200080, People's Republic of China.
J Cancer Res Clin Oncol. 2021 Nov;147(11):3225-3243. doi: 10.1007/s00432-021-03730-3. Epub 2021 Jul 14.
FOXA1, as a pioneering transcription factor, has been shown to drive prostate cancer progression. Previous studies showed that FOXA1 expression in prostate cancer was positively associated with cancer angiolymphatic invasion and metastasis. However, the mechanism underlying the correlation between FOXA1 and prostate cancer angiolymphatic invasion and metastasis remains largely unclear.
Herein, we set out to investigate the role of FOXA1 in the interactions between prostate cancer cells and endothelial cells. Endothelial cells' phenotypes were assessed through CCK-8 assay, Transwell migration assay, and tube formation assay. The angiogenic factors acting on endothelial cells mediated by FOXA1were characterized by RNA-seq, qPCR array, angiogenesis cytokines array, and ELISA assay. The impact of FOXA1 on tumor angiogenesis was examined in a xenograft model in nude mice. The effect of FOXA1 on prostate cancer angiogenesis was validated on a primary prostate cancer tissue microarray.
FOXA1 expression in prostate cancer cells promoted endothelial cell proliferation, migration, and tube formation in vitro. Mechanistically, FOXA1 increased pro-angiogenic factors production, including EGF, Endothelin-1, and Endoglin. Moreover, in vivo study showed that FOXA1 facilitated tumor angiogenesis. Furthermore, clinical samples investigation indicated that FOXA1 enhanced prostate cancer angiogenesis.
Overall, these findings illustrated a tumor angiogenesis-promoting role of FOXA1 in prostate cancer.
FOXA1 作为一种先驱转录因子，已被证明能促进前列腺癌的进展。先前的研究表明，FOXA1 在前列腺癌中的表达与癌症的血管淋巴管浸润和转移呈正相关。然而，FOXA1 与前列腺癌血管淋巴管浸润和转移之间的相关性的机制在很大程度上仍不清楚。
本研究旨在探讨 FOXA1 在前列腺癌细胞与内皮细胞相互作用中的作用。通过 CCK-8 测定、Transwell 迁移测定和管形成测定评估内皮细胞的表型。通过 RNA-seq、qPCR 阵列、血管生成细胞因子阵列和 ELISA 测定来描述 FOXA1 作用于内皮细胞的血管生成因子。在裸鼠异种移植模型中检查 FOXA1 对肿瘤血管生成的影响。在原发性前列腺癌组织微阵列上验证 FOXA1 对前列腺癌血管生成的影响。
前列腺癌细胞中的 FOXA1 表达促进了内皮细胞的增殖、迁移和体外管形成。从机制上讲，FOXA1 增加了促血管生成因子的产生，包括 EGF、内皮素-1 和内格林。此外，体内研究表明 FOXA1 促进了肿瘤血管生成。此外，临床样本研究表明 FOXA1 增强了前列腺癌的血管生成。
总的来说，这些发现说明了 FOXA1 在前列腺癌中具有促进肿瘤血管生成的作用。
