Basement membrane extract attenuates the more malignant gene expression profile accentuated by fibronectin in prostate cancer cells

Abstract

Prostate cancer (PCa) has high mortality rates, with most of the deaths resulting from the development of metastasis. Fibronectin (FN) plays key roles in cell adhesion and affects the migratory behavior of cells. In the tumor microenvironment and also in the blood plasma during metastasis, FN displays increased expression, however its role in prostate cancer remains poorly understood. This study aimed to unveil the specific roles of FN as a soluble component, alone or in combination with a complex basement membrane. To investigate the impact of FN in neoplastic prostate cells, we evaluated the gene expression of LNCaP cells by RT-qPCR after exposure to soluble FN (25 µg/mL) either alone or in combination with a basement membrane. When FN was the predominant matrix element, such as in blood plasma, PCa tumor cells increased their expression of genes related to an invasive behavior and resistance to apoptosis, including CDH2, ITGA5, AKT1, and BCL2. However, the combined presence of FN and a complex basement membrane had the opposite effect on LNCaP cells, in which the expression levels of CDH2, ITGA5, AKT1, and BCL2 were reduced. Hierarchical clustering analysis with LNCaP and RWPE-1 cells showed that LNCaP cells exposed to an enriched extracellular matrix displayed an expression pattern more similar to that shown by RWPE-1 cells, a cell line that illustrates characteristics of the normal prostate epithelium. These findings provide the groundwork for future studies addressing the role of FN in tumor growth, particularly in the context of cancer evolution/progression from a solid primary tumor to a transitory circulating state.

Potent Suppression of Prostate Cancer Cell Growth and Eradication of Cancer Stem Cells by CD44-targeted Nanoliposome-quercetin Nanoparticles

“…It was observed that both quercetin and nanoliposomal formulations suppressed the protein expression of N-cadherin and fibronectin across all treated cells. Martinucci et al [ 50 ] proposed that elevated fibronectin expression levels in prostate cancer cells are associated with increased invasiveness via N-cadherin and integrins, potentially contributing to resistance against apoptosis by upregulating Bcl-2 expression while downregulating Bax expression. Drawing from this insight, it can be inferred that the suppression of fibronectin expression partially contributes to the increase in Bax mRNA levels, which are associated with apoptosis, and the decrease in Bcl-2 protein expression.…”

Fibronectin Modulates the Expression of miRNAs in Prostate Cancer Cell Lines

“…In the present study, we analyzed the impact of FN on the expression of miRNAs in the neoplastic prostate cell lines LNCaP and PC-3, which are widely employed in PCa research. The seven miRNAs examined regulate genes that are known to display altered expression in response to FN exposure ( 13 ).…”

“…Cells were seeded at 4 × 10 4 cells/cm 2 and exposed to human plasma derived FN (Sigma-Aldrich; F0895) at a concentration of 25 μg/ml, according to a protocol previously established ( 13 , 24 ). The experiments were carried out in triplicates.…”

“…FN confers cell advantages as a scaffold for cell invasion and the growth of new blood vessels, as well as increases cell proliferation (10)(11)(12). Our research group has previously shown that LNCaP cells, a neoplastic prostate cell line, display an altered expression of genes involved in cell adhesion, survival, and proliferation when exposed to FN (13).…”

Identification of crucial genes associated with lung adenocarcinoma by bioinformatic analysis

“…[ 15 – 17 ] Cell adhesion is the key to invasion and metastasis of cancer. [ 18 , 19 ] Increasing number of researches and experiments have found that cell adhesion molecules are closely linked to lung cancer. [ 20 , 21 ] Angiogenesis exists in the whole development courses and progression of malignant tumors and is closely related to tumor development, invasion and metastasis.…”