The Role of Neuropilin in Breast Cancer Metastasis
Abstract
The authors have previously implicated neuropilin-1 (NP1), a receptor for vascular endothelial growth factor (VEGF), in an autocrine survival pathway in breast carcinoma cells. Because NP1 promotes tumor cell survival, the goal of this proposal was to address the importance of NP1 in breast cancer progression. They have shown that NP1 is not preferentially expressed in highly aggressive and metastatic breast tumors. They also have demonstrated that the NP1 cytoplasmic domain is not required for its downstream signaling events. To explore the significance of NP1 on breast cancer progression in vivo, the authors attempted to use RNA interference to generate NP1-deficient cell lines. This strategy has been unsuccessful, presumably due to a critical requirement for NP1 expression in the survival of these cells. To circumvent this problem and to study signaling upstream of the NP1 receptor, they generated an alpha6beta4 integrin-deficient breast carcinoma cell line. Because alpha6beta4 regulates VEGF translation, the expression of VEGF is decreased in this cell line. Injection of this integrin-deficient cell line into mice produced significantly fewer orthotopic tumors compared to control cells because of increased apoptosis. The authors have demonstrated that this increased apoptosis correlates with decreased VEGF expression in vivo and presumably loss of NP1-mediated autocrine survival signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA442223
Entities
People
- Elizabeth A. Lipscomb
Organizations
- Beth Israel Deaconess Medical Center