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Non-caveolar caveolin-1 expression in prostate cancer cells promotes lymphangiogenesis.

Nassar ZD, Hill MM, Parton RG, Francois M, Parat MO - Oncoscience (2015)

Bottom Line: The effect of PCa cell conditioned media on lymphatic endothelial cell (LEC) viability, chemotaxis, chemokinesis and differentiation was assessed.In contrast, caveolar Cav-1 (in DU145 cells) did not significantly affect PCa cell lymphangiogenic potential.The effect of non-caveolar Cav-1 on LECs was mediated by increased expression of VEGF-A as demonstrated by neutralization by anti-VEGF-A antibody.

View Article: PubMed Central - PubMed

Affiliation: The University of Queensland, School of Pharmacy, QLD, Australia.

ABSTRACT
Lymphangiogenesis allows prostate cancer (PCa) lymphatic metastasis, which is associated with poor prognosis and short survival rates. Caveolin-1 (Cav-1) is a membrane protein localized in caveolae, but also exists in non-caveolar, cellular or extracellular forms. Cav-1 is overexpressed in PCa, promotes prostate tumour progression and metastasis. We investigated the effect of caveolar and non-caveolar Cav-1 on PCa lymphangiogenic potential. Cav-1 was down-regulated in PC3 and DU145, and ectopically expressed in LNCaP cells. The effect of PCa cell conditioned media on lymphatic endothelial cell (LEC) viability, chemotaxis, chemokinesis and differentiation was assessed. The effect of Cav-1 on PCa cell expression of lymphangiogenesis-modulators VEGF-A and VEGF-C was assessed using qPCR and ELISA of the conditioned medium. Non-caveolar Cav-1, whether exogenous or endogenous (in LNCaP and PC3 cells, respectively) enhanced LEC proliferation, migration and differentiation. In contrast, caveolar Cav-1 (in DU145 cells) did not significantly affect PCa cell lymphangiogenic potential. The effect of non-caveolar Cav-1 on LECs was mediated by increased expression of VEGF-A as demonstrated by neutralization by anti-VEGF-A antibody. This study unveils for the first time a crucial role for non-caveolar Cav-1 in modulating PCa cell expression of VEGF-A and subsequent LEC proliferation, migration and tube formation.

No MeSH data available.


Related in: MedlinePlus

Effect of Cav-1 expression in prostate cancer cells on secretome-modulated LEC viabilityLEC viability after 48 h exposure to prostate cancer cell-conditioned media was assessed using the MTT assay. Results are reported as percent of LEC viability compared to the control PCa cell conditioned medium and shown as mean ± S.E.M. (n=3 separate experiments), *p<0.05.
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Figure 2: Effect of Cav-1 expression in prostate cancer cells on secretome-modulated LEC viabilityLEC viability after 48 h exposure to prostate cancer cell-conditioned media was assessed using the MTT assay. Results are reported as percent of LEC viability compared to the control PCa cell conditioned medium and shown as mean ± S.E.M. (n=3 separate experiments), *p<0.05.

Mentions: The effect of prostate cancer cell-conditioned medium on LEC proliferation was evaluated by the MTT assay. Ectopic expression of Cav-1 in LNCaP cells enhanced LEC proliferation significantly compared to cells exposed to the CM of control cells. Similarly, LECs exposed to the conditioned medium of Cav-1-down-regulated PC3 cells showed significantly less proliferation than LECs treated with the CM of control cells expressing endogenous Cav-1. In contrast, down-regulation of Cav-1 expression in DU145 cells only marginally lowered LEC viability, and the change was not statistically significant (Figure 2). These results indicate that Cav-1 expression in LNCaP and PC3, but not in DU145, promotes LEC proliferation.


Non-caveolar caveolin-1 expression in prostate cancer cells promotes lymphangiogenesis.

Nassar ZD, Hill MM, Parton RG, Francois M, Parat MO - Oncoscience (2015)

Effect of Cav-1 expression in prostate cancer cells on secretome-modulated LEC viabilityLEC viability after 48 h exposure to prostate cancer cell-conditioned media was assessed using the MTT assay. Results are reported as percent of LEC viability compared to the control PCa cell conditioned medium and shown as mean ± S.E.M. (n=3 separate experiments), *p<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549361&req=5

Figure 2: Effect of Cav-1 expression in prostate cancer cells on secretome-modulated LEC viabilityLEC viability after 48 h exposure to prostate cancer cell-conditioned media was assessed using the MTT assay. Results are reported as percent of LEC viability compared to the control PCa cell conditioned medium and shown as mean ± S.E.M. (n=3 separate experiments), *p<0.05.
Mentions: The effect of prostate cancer cell-conditioned medium on LEC proliferation was evaluated by the MTT assay. Ectopic expression of Cav-1 in LNCaP cells enhanced LEC proliferation significantly compared to cells exposed to the CM of control cells. Similarly, LECs exposed to the conditioned medium of Cav-1-down-regulated PC3 cells showed significantly less proliferation than LECs treated with the CM of control cells expressing endogenous Cav-1. In contrast, down-regulation of Cav-1 expression in DU145 cells only marginally lowered LEC viability, and the change was not statistically significant (Figure 2). These results indicate that Cav-1 expression in LNCaP and PC3, but not in DU145, promotes LEC proliferation.

Bottom Line: The effect of PCa cell conditioned media on lymphatic endothelial cell (LEC) viability, chemotaxis, chemokinesis and differentiation was assessed.In contrast, caveolar Cav-1 (in DU145 cells) did not significantly affect PCa cell lymphangiogenic potential.The effect of non-caveolar Cav-1 on LECs was mediated by increased expression of VEGF-A as demonstrated by neutralization by anti-VEGF-A antibody.

View Article: PubMed Central - PubMed

Affiliation: The University of Queensland, School of Pharmacy, QLD, Australia.

ABSTRACT
Lymphangiogenesis allows prostate cancer (PCa) lymphatic metastasis, which is associated with poor prognosis and short survival rates. Caveolin-1 (Cav-1) is a membrane protein localized in caveolae, but also exists in non-caveolar, cellular or extracellular forms. Cav-1 is overexpressed in PCa, promotes prostate tumour progression and metastasis. We investigated the effect of caveolar and non-caveolar Cav-1 on PCa lymphangiogenic potential. Cav-1 was down-regulated in PC3 and DU145, and ectopically expressed in LNCaP cells. The effect of PCa cell conditioned media on lymphatic endothelial cell (LEC) viability, chemotaxis, chemokinesis and differentiation was assessed. The effect of Cav-1 on PCa cell expression of lymphangiogenesis-modulators VEGF-A and VEGF-C was assessed using qPCR and ELISA of the conditioned medium. Non-caveolar Cav-1, whether exogenous or endogenous (in LNCaP and PC3 cells, respectively) enhanced LEC proliferation, migration and differentiation. In contrast, caveolar Cav-1 (in DU145 cells) did not significantly affect PCa cell lymphangiogenic potential. The effect of non-caveolar Cav-1 on LECs was mediated by increased expression of VEGF-A as demonstrated by neutralization by anti-VEGF-A antibody. This study unveils for the first time a crucial role for non-caveolar Cav-1 in modulating PCa cell expression of VEGF-A and subsequent LEC proliferation, migration and tube formation.

No MeSH data available.


Related in: MedlinePlus