Related Experiment Video
Updated: Jun 24, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Role of the VEGFR3/VEGFD receptor axis in TGFbeta1 activation of primary prostate cell lines
S M Goodyear1, S B Kheyfets, F U Garcia
1Molecular Pathobiology Program, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102-1192, USA.
Background:
Reports indicate that vascular endothelial growth factor receptor type 3 (VEGFR3) regulates cellular functions such as invasion, proliferation, and chemo-resistance. However, the exact function of the VEGFR3 signaling axis in prostate epithelial cells is poorly characterized.
Methods:
The goal of this study was to evaluate whether TGFbeta1 in combination with VEGFD can promote pre-malignant invasive activities of intermediate basal cells (IBC-10a) isolated from human prostate cancer (Gleason score 6).
Results:
hTERT immortalized IBC-10a cells normally grew as confluent "cobblestoned" monolayers, but treatment with TGFbeta1 (10 ng/ml for 2-6 hr) dissociated the cell-cell junctions and induced VEGFR3 translocation to the cell surface. This event was not inhibited by 10 microM cycloheximide or puromycin, indicating transcription and protein synthesis were not required. We further discovered that TGFbeta1 in combination with VEGFD induced a significant increase in the invasive activity of IBC-10a cells (>26% and 53% after 24 and 48 hr, respectively) in modified Boyden Chamber assays. TGFbetaRII receptor antibodies specifically blocked TGFbeta1 induction of VEGFR3 translocation to the cell surface and blocked VEGFD-induced invasion. Zymograms revealed that TGFbeta1 (and not VEGFR3) stimulated the secretion of MMP-2 and MMP-9, presumably to promote cell invasion. The cell invasion assays confirmed that antibodies specific for TGFbetaII receptor, MMP-2 and MMP-9 and VEGFR3, independently blocked TGFbeta1-induced invasion.
Conclusions:
For the first time, we have demonstrated the mechanism by which TGFbeta1 stimulates VEGFD/VEGFR3 receptor axis activation leading to increased cell migration and invasion by primary intermediate basal cell cultures.
Insights
Transforming growth factor beta1 (TGFbeta1) activates vascular endothelial growth factor receptor type 3 (VEGFR3) signaling in prostate cancer cells, promoting invasion. This pathway involves matrix metalloproteinases and offers potential therapeutic targets.
Area of Science:
- Prostate cancer research
- Cell signaling pathways
- Molecular oncology
Background:
- Vascular endothelial growth factor receptor type 3 (VEGFR3) is implicated in cellular functions like invasion and proliferation.
- The specific role of the VEGFR3 signaling axis in prostate epithelial cells remains unclear.
Purpose of the Study:
- To investigate if TGFbeta1 combined with VEGFD promotes pre-malignant invasive activities in human prostate cancer intermediate basal cells (IBC-10a).
Main Methods:
- Treatment of IBC-10a cells with TGFbeta1 and VEGFD.
- Analysis of VEGFR3 translocation, cell-cell junction dissociation, and invasive activity using modified Boyden Chamber assays.
- Assessment of matrix metalloproteinase (MMP) secretion via zymography.
Main Results:
- TGFbeta1 induced VEGFR3 translocation to the cell surface, independent of protein synthesis.
- TGFbeta1 and VEGFD significantly increased IBC-10a cell invasion, blocked by TGFbetaRII receptor antibodies.
- TGFbeta1 stimulated MMP-2 and MMP-9 secretion, contributing to cell invasion.
Conclusions:
- TGFbeta1 activates the VEGFD/VEGFR3 axis in prostate cancer cells.
- This activation leads to increased cell migration and invasion.
- The study elucidates a novel mechanism of TGFbeta1-induced prostate cancer cell invasion.
Related Concept Videos
01:16TGF - β Signaling Pathway
01:24Regulation of Angiogenesis and Blood Supply