Thursday, November 8, 2007 - 12:50 PM
577b

Quantitative Analysis of the Effects of Vegf-Signaling on Bone Marrow-Derived Cell Recruitment and Accumulation in Lung Metastases

Michelle R. Dawson, Dan G. Duda, and Rakesh K. Jain. Department of Radiation Oncology, Edwin L. Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, 100 Blossom Street, Cox 7, Boston, MA 02114

Recent studies have shown that bone marrow derived cells (BMDCs) are critical for the formation of lung metastases (Nature, 2005). In theses studies, Kaplan et al showed that BMDCs infiltrated the lungs of tumor-bearing mice prior to the arrival of tumor cells. They found that blocking the infiltration of BMDCs prevented the formation of metastases. In similar studies, we have recently found that BMDCs contribute to lung metastasis' functional vasculature (Blood, 2006), and that treatment with vascular endothelial growth factor receptor 1 (VEGFR1)-blocking antibody (MF1) limits their accumulation in the lungs of tumor-bearing mice (unpublished results). Using confocal microscopy and image analysis software, we quantified the effects of VEGF-receptor blockade on the recruitment and accumulation of BMDCs in the primary tumor and lungs of immunocompetent mice (first irradiated and rescued by transplanting bone marrow from transgenic mice constitutively expressing green fluorescent protein). This study provides quantitative analysis of the kinetics of bone marrow cell accumulation in primary and metastatic tumors.


Web Page: steele.mgh.harvard.edu/cv/michelle.htm