Normal Basal Epithelial Cells Stimulate the Migration and Invasion of Prostate Cancer Cell RM-1 by TGF-β1/STAT3 Axis in vitro

Abstract

Aim Basal epithelial cells are absent in distant prostate cancer. This study aimed to investigate whether basal epithelial cells could suppress migration and invasion of prostate cancer cells to become a new treatment strategy for prostate cancer. Main Methods Basal epithelial cells were identified by immunofluorescence with anti-p63. Wound healing assays or transwell assays were used to explore the effects of basal epithelial cells, TGF-β1, SB431542 (inhibitor of TGF-β type I receptor) or stattic (inhibitor of phosphorylated STAT3) on migration or invasion of mouse prostate cancer cell (RM-1). Concentration of TGF-β1 was measured by ELISA assay. HE staining was used to investigate cell morphology. Immunocytochemistry with anti-p63 was used to identify basal epithelial cells. Levels of STAT3, p-STAT3 (Ser727) and proteins associated with EMT were measured with Western blot assay. Cell proliferation was measured with MTT or CCK8 assay. Results Normal basal epithelial cells acquired from mouse prostate were specific to anti-p63 and more than 90%. Basal epithelial cells and RM-1 could both secrete TGF-β1. Basal epithelial cells and TGF-β1 promoted the migration and invasion of RM-1 through changing the cell morphology and up-regulating expression of ZEB1, N-cadherin, vimentin, snail and p-STAT3 (Ser727), at the same time down-regulating E-cadherin of RM-1. SB431542 strongly suppressed migration, invasion as well as the expressions of EMT relevant proteins and p-STAT3 (Ser727) of co-cultured RM-1. In addition, stattic suppressed proliferation, migration and invasion of non-treated RM-1 and co-cultured RM-1. Conclusion Our study suggests that normal basal epithelial cells might stimulate the migration and invasion of RM-1 by TGF-β1/STAT3 axis which could be suppressed by inhibitor of TGF-β receptor and inhibitor of p-STAT3. So, basal epithelial cells might not become a treatment strategy for prostate cancer, but our results could provide some researching references for other diseases which include basal epithelial cells such as prostatic intraepithelial neoplasia, prostatic hyperplasia, cervical cancer, or urinary bladder cancer.

Adapalene Inhibits Prostate Cancer Cell Proliferation In Vitro and In Vivo by Inducing DNA Damage, S-phase Cell Cycle Arrest, and Apoptosis

“…There are some deficiencies in our research. Although many biological functions and behavior of RM-1 cells with prostate cancer model are close to human cells ( Li et al, 2021 ), our results can not completely represent the effects of ADA in human prostate cancer cells, and further research should be combined with human prostate cancer cell experiments in the future.…”

STAT3 and Its Pathways Dysregulation – Underestimated Role in Urological Tumors

“…Calcitriol used as a treatment decreased STAT3 phosphorylation [35,36]. STAT3 was proven to affect cell metabolism by upregulated glucose consumption and lactate production in bladder cancer by enhanced transcription of LDHA, ENO2, HK2 and IGFBP3 [37,39].…”

“…Lastly, induced expression of PD-L1 helps a tumor to avoid physiological immune response[36]. Collectively, high expression and activation of STAT3 result in increased cell survival, proliferation, angiogenesis, invasion and migration, leading to distal metastasis[37][38][39].Tumors might be described as complicated organs which consist of not only tumorous cells, but also benign cells, e.g. stromal cells.…”

Current understanding of prostate cancer biomarkers

“…В последние годы во многом благодаря развитию геномных технологий достигнут значительный прогресс в изучении новых биомаркеров РПЖ в различных биологических средах (моче, крови, тканях) [9][10][11]. Большинство современных биомаркеров представляют собой комплекс из нескольких маркеров, объединенных в формулу или под общим названием.…”