Abnormal tumor vasculatures and bone marrow-derived pro-angiogenic cells in cancer

Tumor-derived factors affect the stroma of cancer tissue by activating pro-angiogenic signals. One of the key components of this response is the mobilization of the pro-angiogenic cells from bone marrow (BM), which contribute to the development of abnormal tumor vasculature. Evidence is accumulating that the pro-angiogenic cells derived from BM are involved in the physiological processes of tissue repair and wound healing. However, vascular structure in cancer tissue is impaired, resulting in the formation of chaotic neo-vessels and hypoxic microenvironments. Ultimately, these structural and functional abnormalities result in the limited delivery of chemotherapeutic agents and create regions of metabolic derangement, both of which enhance resistance to chemotherapy. In spite of recent advances in targeted therapy using anti-vascular agents, clinical results from studies using individual agents have unsatisfactory, necessitating the combinatorial use of anti-cancer drugs and a targeting agent. We suggest the possibility of a new therapeutic approach in which aberrant tumor vessels are normalized by BM-derived pro-angiogenic cells, and the delivery of anti-cancer drugs is maximized. In this review, we focus on the current understanding of the structure and function of tumor vessels, and an alternative approach to the repair of abnormal tumor vasculature by the use of BM-derived pro-angiogenic cells. This approach may improve both the delivery and the efficacy of anti-cancer drugs by restoring aberrant tumor vascularization and hypoxia.