Chakraborty, Goutam ; Jain, Shalini ; Kundu, Gopal C. (2008) Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms Cancer Research, 68 (1). pp. 152-161. ISSN 0008-5472
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Official URL: http://cancerres.aacrjournals.org/content/68/1/152...
Related URL: http://dx.doi.org/10.1158/0008-5472.CAN-07-2126
Abstract
Angiogenesis is the hallmark of cancer, and development of aggressiveness of primary tumor depends on de novo angiogenesis. Here, using multiple in vitro and in vivo models, we report that osteopontin (OPN) triggers vascular endothelial growth factor (VEGF)-dependent tumor progression and angiogenesis by activating breast tumor kinase (Brk)/nuclear factor-inducing kinase/nuclear factor-κB (NF-κB)/activating transcription factor-4 (ATF-4) signaling cascades through autocrine and paracrine mechanisms in breast cancer system. Our results revealed that both exogenous and tumor-derived OPN play significant roles in VEGF-dependent tumor angiogenesis. Clinical specimen analysis showed that OPN and VEGF expressions correlate with levels of neuropilin-1, Brk, NF-κB, and ATF-4 in different grades of breast cancer. Consequently, OPN plays essential role in two key aspects of tumor progression: VEGF expression by tumor cells and VEGF-stimulated neovascularization. Thus, targeting OPN and its regulated signaling network could be a novel strategy to block tumor angiogenesis and may develop an effective therapeutic approach for the management of breast cancer.
Item Type: | Article |
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Source: | Copyright of this article belongs to American Association for Cancer Research. |
Keywords: | Breast Cancer; Signal Transduction; Cell Motility and Migration; Angiogenic Factors and Receptors; Xenograft Models |
ID Code: | 19965 |
Deposited On: | 20 Nov 2010 15:14 |
Last Modified: | 17 May 2016 04:25 |
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