The Role of Neuropilin in Breast Cancer Metastasis
Abstract
Our group has recently characterized a novel autocrine survival pathway in breast carcinoma cells mediated by vascular endothelial growth factor binding to neuropilin-1 and stimulation of the phosphatidylinositol 3 -kinase pathway. The goal of this proposal is to define the mechanism by which neuropilin-l contributes to the survival and metastasis of breast carcinoma cells. Because neuropilin-1 promotes tumor cell survival, we hypothesize that neuropilin-1 plays a critical role in breast cancer metastasis. To investigate this hypothesis, the expression of neuropilin- 1 in human breast tumors was examined as a function of disease progression. We found that neuropilin-1 was expressed at a low level in tumor cells but that the level of neuropilin-1 did not increase with disease progression. In addition, our current data suggest that the cytoplasmic domain of neuropilin- 1 does not play a role in its pro-survival function. To investigate the ability of neuropilin-1 to directly promote spontaneous metastasis in vivo, we have generated a cell line that constitutively downregulates neuropilin-1 expression. Future studies using this cell line will explore the importance of neuropilin- 1 expression in vivo for the progression of tumorigenic breast carcinoma cells to the metastatic phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA418890
Entities
People
- Arthur M Mercurio
- Elizabeth A. Libscomb
Organizations
- Beth Israel Deaconess Medical Center