1588P - Caveolin-1 modulates VEGF-A and VEGF-C expression and enhances prostate cancer lymphangiogenesis potential

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Prostate Cancer
Translational Research
Presenter Zeyad Nassar
Citation Annals of Oncology (2014) 25 (suppl_4): iv546-iv563. 10.1093/annonc/mdu358
Authors Z.D. Nassar1, M. Francois2, R.G. Parton2, M.O. Parat1
  • 1School Of Pharmacy, University of Queensland, 4102 - Brisbane/AU
  • 2Institute For Molecular Bioscience, University of Queensland, 4067 - Brisbane/AU



Lymphatic metastasis in prostate cancer is associated with poor prognosis and short free survival rates. Hence, understanding the mechanisms of lymphatic metastasis is vital to comprehending the progression of the disease and to expanding the available therapeutic options. Lymphatic metastasis relies on lymphangiogenesis. Strong evidence shows that caveolin-1 (Cav-1) promotes prostate cancer growth, drug resistance and metastasis. This study aims to evaluate the effect of Cav-1 expression in prostate cancer cells on lymphangiogenesis.


Cav-1 was ectopically expressed in LNCaP cells and down regulated in PC3 cells. Lymphatic endothelial cells (LECs) generated previously from H-2Kb-tsA58 mouse mesentery were used in this study. The effect of prostate cancer cell conditioned media on LEC proliferation, migration and differentiation to tube-like structures was evaluated using the MTT, modified Boyden chamber, and tube formation assays, respectively. The effect of Cav-1 expression on matrix metalloproteinase-9 (MMP-9) activity was investigated using in-gel zymography. In addition, the effect of Cav-1 expression on the production of lymphangiogenesis-driving growth factors VEGF-A and VEGF-C by prostate cancer cells was assessed using real time RT-PCR.


Exogenous expression of Cav-1 in LNCaP cells enhanced LECs proliferation, migration and differentiation when compared with control LNCaP cells. Likewise, LECs exposed to the conditioned medium of Cav-1–down regulated PC3 cells proliferated, migrated and differentiated into tube-like structure faster than those exposed to conditioned medium of control PC3 cells. Down-regulation of Cav-1 in PC3 decreased MMP-9 activity by 40.04 %±11.19 (P=0.025). Real time RT-PCR results revealed that Cav-1 expression in LNCaP cells increased the expression of VEGF-A by 1.839±0.30 (P=0.0199) fold. The loss of Cav-1 expression in PC3 cells resulted in attenuation of the VEGF-A and VEGF-C expression by 1.653±0.01 (P=0.0028) and 1.95±0.035 (P< 0.0001) fold, respectively.


This study shows that endogenously or exogenously expressed Cav-1 in prostate cancer cells plays a crucial role in modulating the expression of lymphangiogenesis growth factors VEGF-A and VEGF-C and subsequently LEC proliferation, migration and tubule formation.


All authors have declared no conflicts of interest.