Estrogen Mobilizes Circulating Bone Marrow Progenitor Cells to Promote Tumor Neovasculature: Lessions from Ischemic Model Provide a Novel Breast Cancer Target.

摘要

Breast cancer growth and metastases is dependent on neovasculature. The cells that actually trigger the formation of new blood vessels are poorly characterized but it has been hypothesized that some of the precursor blood vessel cells originate in the bone marrow and then home to tumor tissues. Although estrogen is a major stimulus, its role as a bone marrow originating endothelial cell mobilizing agent has not been demonstrated. We propose to test the proposition whether estrogen can mobilize circulating bone marrow derived progenitor endothelial cells (EPCs) to the implanted tumor using Green fluorescence protein, GFP, tagged EPCs. The objectives of the proposed study are two fold: A) Establishment of proposed Animal model using normal and OVX (ovariectomized) female BALB/c mice and examine if estrogen can indeed mobilize the EPCs for the generation of new blood vessels. B) To elucidate the contribution of E2-mobilized, BM-derived EPC in promoting neo-vascularization in implanted breast tumor. The mechanism of E2-induced mobilization of EPC from the bone marrow will open a new area of BrCa research and hence novel targets. Moreover, BM-EPCS could potentially serve as the 'Trojan horse' to deliver bio- molecules that disrupt tumor vasculogenesis and/or induce targeted killing of tumor cells. Thus this novel basic concept has clinical potential.