Cancers 2013, 5(2), 617-638; doi:10.3390/cancers5020617
Article

Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells

,  and * email
Received: 4 March 2013; in revised form: 14 April 2013 / Accepted: 15 May 2013 / Published: 27 May 2013
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Osteopontin and MMP9 are implicated in angiogenesis and cancer progression. The objective of this study is to gain insight into the molecular mechanisms underlying angiogenesis, and to elucidate the role of osteopontin in this process. We report here that osteopontin/αvβ3 signaling pathway which involves ERK1/2 phosphorylation regulates the expression of VEGF. An inhibitor to MEK or curcumin significantly suppressed the phosphorylation of ERK1/2 and expression of VEGF. MMP9 knockdown reduces the secretion but not the expression of VEGF. Moreover, MMP9 knockdown increases the release of angiostatin, a key protein that suppresses angiogenesis. Conditioned media from PC3 cells treated with curcumin or MEK inhibitor inhibited tube formation in vitro in human microvascular endothelial cells. Similar inhibitory effect on tube formation was found with conditioned media collected from PC3 cells expressing mutant-osteopontin at integrin-binding site and knockdown of osteopontin or MMP9. We conclude that MMP9 activation is associated with angiogenesis via regulation of secretion of VEGF and angiostatin in PC3 cells. Curcumin is thus a potential drug for cancer treatment because it demonstrated anti-angiogenic and anti-invasive properties.
Keywords: osteopontin; integrin αvβ3; MMP9; VEGF; angiogenesis; curcumin
PDF Full-text Download PDF Full-Text [1715 KB, uploaded 27 May 2013 12:23 CEST]

Export to BibTeX |
EndNote


MDPI and ACS Style

Gupta, A.; Zhou, C.Q.; Chellaiah, M.A. Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells. Cancers 2013, 5, 617-638.

AMA Style

Gupta A, Zhou CQ, Chellaiah MA. Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells. Cancers. 2013; 5(2):617-638.

Chicago/Turabian Style

Gupta, Aditi; Zhou, Cindy Q.; Chellaiah, Meenakshi A. 2013. "Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells." Cancers 5, no. 2: 617-638.

Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert