Imaging CXCL12-CXCR4 Signaling and Inhibition in Ovarian Cancer
Revised annual rept. 1 Jul 2010-30 Jun 2011
MICHIGAN UNIV ANN ARBOR
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CXCR4 and its chemokine ligand CXCL12 may represent new molecular targets for chemotherapy in patients with ovarian cancer. CXCR4 is expressed on ovarian cancer cells in approximately 50 of patients, and expression of this receptor correlates with poor prognosis. High levels of CXCL12 are present in ascites of patients with ovarian cancer, providing a local source of chemokine ligand in the tumor microenvironment. CXCL12 signaling through CXCR4 activates pathways that could promote tumor growth, dissemination, and resistance to chemotherapy. However, our knowledge of how these signaling pathways function in the tumor microenvironment of ovarian cancer in vivo is poorly understood. We propose to develop new molecular imaging technologies and signaling reporters to analyze CXCR4 signaling in vivo and determine to what extent inhibiting CXCL 12-CXCR4 signaling produces disease regression in mouse models of ovarian cancer.
- Anatomy and Physiology
- Medicine and Medical Research