Abstract
ABSTRACTThe most prominent cancer-associated fibroblasts (CAFs) in tumor stroma is known to form a protective structure to support tumor growth. Anterior gradient-2 (AGR2), a tumor secretory protein is believed to play a pivotal role during tumor microenvironment (TME) development. Here, we report that extracellular AGR2 enhances fibroblasts elongation and migration significantly. The early stimulation of RhoA showed the association of AGR2 by upregulation of G1-S phase-regulatory protein cyclin D1 and FAK phosphorylation through fibroblasts growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR). Our finding indicates that secretory AGR2 alters fibroblasts elongation, migration, and organization suggesting the secretory AGR2 as a potential molecular target that might be responsible to alter fibroblasts infiltration to support tumor growth.
Highlights
Tumour microenvironment (TME) consists of complex interactions of tumour cells with the extracellular matrix (ECM)
Extracellular Anterior gradient-2 (AGR2) increases the chemotaxis of NIH3T3 cells through fibroblasts growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR) under soft agar DMEM (saDMEM)
We first examined the effect of AGR2, basic fibroblast growth factor (bFGF), and AGR2 coupled with bFGF on NIH3T3 cells chemotaxis by exposing cells to temporal dynamic concentration gradient in saDMEM semisolid medium
Summary
Tumour microenvironment (TME) consists of complex interactions of tumour cells with the extracellular matrix (ECM) These phenomena are regulated by the exchange of biophysical and biochemical factors which contribute to detachment, migration, proliferation, invasion, and re-attachment of the cells present in TME [1]. Cancer cells secrete various molecules like transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1) and interleukin-6 [8,9,10,11,12]. These tumour niche secretome plays a pivotal role in cellular communications and regulates stromal fibroblasts to support tumour growth [13]
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