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Investigating the role of Matrix Metalloproteinase-9 (MMP9), Vascular Endothelial Growth Factor (VEGF) on Breast Cancer Metastasis to the Spine

Support: Johns Hopkins Medical Student Research Grant
Principle Investigator: D.M. Sciubba

Project Overview

The spine is a common site for cancer metastasis, and the disease process is often discovered when patients manifest functional impairments or severe pain secondary to compression fractures. Sadly, metastatic lesions in the bony spine are often discovered at advanced stages, when patients are no longer candidates for aggressive surgical or medical options. Research into metastatic disease has started to focus on the genetic mechanisms governing cancer spread to distant sites in the body, with an emphasis on gene signatures that can be assessed in the primary tumor.

We hypothesize that metastatic breast cancer lesions isolated from the spines of human patients will demonstrate increased MMP9 and VEGF expression compared to normal bone. We further hypothesize that cells from these metastatic lesions will prove viable in cell culture, enabling us to establish an in vitro database of human metastatic cancer cells. We believe these cells will proliferate in an experimental mouse when introduced to the systemic circulation. Finally, we propose that targeted inhibition of MMP9 and VEGF will reduce the incidence of metastatic lesions in the spine of experimental animals, allowing a potential option for treating human patients afflicted with the same condition.

Radiographic evidence of bony involvement

Radiographic evidence of bony involvement (white circles) in mouse
model of metastatic mammary adenocarcinoma as described by Lau
et al. Borrowed from Lau et al., Int J Cancer Aug 2009

 

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