Journal article
Role of the VEGFR3/VEGFD Receptor Axis in TGF beta 1 Activation of Primary Prostate Cell Lines
The Prostate, v 69(9), pp 982-990
15 Jun 2009
PMID: 19301310
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 TGF beta 1 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 TGF beta 1 (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 mu M cycloheximide or puromycin, indicating transcription and protein synthesis were not required. We further discovered that TGF beta 1 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. TGF beta RII receptor antibodies specifically blocked TGF beta 1 induction of VEGFR3 translocation to the cell surface and blocked VEGFD-induced invasion. Zymograms revealed that TGF beta 1 (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 TGF beta II receptor, MMP-2 and MMP-9 and VEGFR3, independently blocked TGF beta 1-induced invasion.
CONCLUSIONS. For the first time, we have demonstrated the mechanism by which TGF beta 1 stimulates VEGFD/VEGFR3 receptor axis activation leading to increased cell migration and invasion by primary intermediate basal cell cultures. Prostate 69: 982-990, 2009. (C) 2009 Wiley-Liss, Inc.
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Details
- Title
- Role of the VEGFR3/VEGFD Receptor Axis in TGF beta 1 Activation of Primary Prostate Cell Lines
- Creators
- S. M. Goodyear - Drexel UniversityS. B. Kheyfets - Drexel UniversityF. U. Garcia - Drexel UniversityM. E. Stearns - Drexel University
- Publication Details
- The Prostate, v 69(9), pp 982-990
- Publisher
- Wiley
- Number of pages
- 9
- Grant note
- CA07739 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000266470700009
- Scopus ID
- 2-s2.0-67049117684
- Other Identifier
- 991019168854104721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Endocrinology & Metabolism
- Urology & Nephrology