Work

TGFβ1 and RGD Cooperatively Regulate SMAD2/3-Mediated Oncogenic Effects in Prostate Cancer Cells in Bio-Orthogonally Constructed Hydrogels

Year: 2025

Type: article

Abstract: ABSTRACT To recapitulate prostate cancer metastasis, DU145 cells were cultured in a hyaluronic acid-based, bioorthogonally constructed, protease-degradable hydrogel. In the presence of covalently conjugated integrin-binding peptide (G RGD SP), DU145 cells formed tumoroids and exhibited small protrusions. Upon addition of soluble transforming growth factor beta 1 (TGFβ1), cells underwent morphological changes to form extended interconnected cellular networks. Contrarily, in RGD-free hydrogels, cells maintained spherical structures even in the presence of TGFβ1. In RGD-conjugated hydrogels, TGFβ1 induced nuclear localization of SMAD2/3, upregulating a wide range of TGFβ1 target genes and proteins. Prolonged exposure to TGFβ1 led to matrix remodeling and induced epithelial-to-mesenchymal transition in DU145 cells, with loss of epithelial markers and gain of mesenchymal markers. TGFβRI/ALK5 inhibitor SB-431542 attenuated TGFβ1-induced morphological changes, abrogated nuclear localization of SMAD2/3, and restored the expression of key epithelial markers. Our findings highlight the cooperative role of TGFβ1 signaling and integrin binding peptide in the acquisition of aggressive phenotype and promoting tumor progression. TEASER Physiologically relevant 3D cell culture platforms enabled mechanistic investigation of growth factor signaling related to prostate cancer metastasis.

Source: ACS Biomaterials Science & Engineering

DOI: 10.1021/acsbiomaterials.5c00007

Authors: Mugdha Pol, Hanyuan Gao, Joseph M. Fox, Xinqiao Jia

Institution: University of Delaware

Language: English

Topic: TGF-β signaling in diseases

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green