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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 in vitro lymphangiogenesis(A) LEC differentiation into tube-like structures was investigated by plating them on Matrigel− -pre-coated 96-well plates and exposing them to various prostate cancer cell-conditioned media for 4-6 h. The number of branching points was quantified. Results are reported as percent of control PCa cell conditioned medium and shown as mean ± S.E.M. (n=3 separate experiments), *p<0.05. (B) Representative micrographs of tubes formed by LEC exposed to PCa cell-conditioned media.
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Figure 4: Effect of Cav-1 expression in prostate cancer cells on in vitro lymphangiogenesis(A) LEC differentiation into tube-like structures was investigated by plating them on Matrigel− -pre-coated 96-well plates and exposing them to various prostate cancer cell-conditioned media for 4-6 h. The number of branching points was quantified. Results are reported as percent of control PCa cell conditioned medium and shown as mean ± S.E.M. (n=3 separate experiments), *p<0.05. (B) Representative micrographs of tubes formed by LEC exposed to PCa cell-conditioned media.

Mentions: The consequences of Cav-1 expression in prostate cancer cells on their lymphangiogenic potential were further studied using LEC tube formation on Matrigel™. LECs plated on Matrigel™ and exposed to conditioned medium of Cav-1-expressing LNCaP or PC3 cells formed significantly more tubes than LECs exposed to conditioned media of cells with lacking or down-regulated Cav-1 expression. In contrast, alteration of Cav-1 expression in DU145 cells did not significantly alter LEC differentiation into tube-like structures (Figure 4). These results show that Cav-1 expression in LNCaP and PC3 but not in DU145 promotes LEC differentiation.


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 in vitro lymphangiogenesis(A) LEC differentiation into tube-like structures was investigated by plating them on Matrigel− -pre-coated 96-well plates and exposing them to various prostate cancer cell-conditioned media for 4-6 h. The number of branching points was quantified. Results are reported as percent of control PCa cell conditioned medium and shown as mean ± S.E.M. (n=3 separate experiments), *p<0.05. (B) Representative micrographs of tubes formed by LEC exposed to PCa cell-conditioned media.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Effect of Cav-1 expression in prostate cancer cells on in vitro lymphangiogenesis(A) LEC differentiation into tube-like structures was investigated by plating them on Matrigel− -pre-coated 96-well plates and exposing them to various prostate cancer cell-conditioned media for 4-6 h. The number of branching points was quantified. Results are reported as percent of control PCa cell conditioned medium and shown as mean ± S.E.M. (n=3 separate experiments), *p<0.05. (B) Representative micrographs of tubes formed by LEC exposed to PCa cell-conditioned media.
Mentions: The consequences of Cav-1 expression in prostate cancer cells on their lymphangiogenic potential were further studied using LEC tube formation on Matrigel™. LECs plated on Matrigel™ and exposed to conditioned medium of Cav-1-expressing LNCaP or PC3 cells formed significantly more tubes than LECs exposed to conditioned media of cells with lacking or down-regulated Cav-1 expression. In contrast, alteration of Cav-1 expression in DU145 cells did not significantly alter LEC differentiation into tube-like structures (Figure 4). These results show that Cav-1 expression in LNCaP and PC3 but not in DU145 promotes LEC differentiation.

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