Differentiated pre-adipocytes promote proliferation, migration and epithelial-mesenchymal transition in breast cancer cells of different p53 status.

Abstract

Breast cancer progression and metastasis are associated with stromal cells in the tumor microenvironment. Adipocytes are the most abundant cells surrounding breast stromal tissue, promote tumor progression through the induction of Epithelial-to-Mesenchymal Transition (EMT) which is negatively regulated by tumor suppressor protein p53. In this study aimed to investigate the role of p53 in the progression of breast cancer after mature adipocyte-conditioned medium (CM) application. The proliferative effect of CM obtained from differentiated pre-adipocytes were assessed by MTS assay. 20% CM increased cell proliferation in breast cancer cells, T-47D (mutant p53) and MCF-7 (wild-type p53). The migration and invasion capacity were evaluated by scratch and transwell assays, respectively. CM significantly enhanced migration and invasion capacity in T-47D compared to MCF-7. Gene and protein expressions were detected by qRT-PCR and Western Blot analysis, respectively. CM markedly increased expression levels of Cyclin D1, PI3K, MMP9, Snail and Twist in T-47D compared to MCF-7. However, CM did not change E-Cadherin level in T-47D while downregulated in MCF-7 cells. Also, the protein levels of NFκB p65, p-Akt, Snail, and Vimentin were upregulated in both cells. Overall, the findings highlight how the p53 status affects mature adipocyte-mediated proliferation, migration, and aggressive behavior of breast cancer cell lines. Targeting the tumor microenvironment may represent a promising approach for preventing breast cancer progression and metastasis.