Cancer neovascularization and proinflammatory microenvironments.

Tumor neovascularization plays critical roles for the development, progression and metastasis of cancers via utilizing blood flow to supply nutrients and oxygen. Recent cumulative information on biology of tumor neovascularization from both laboratory and clinical studies has opened us to develop new therapeutic approaches to treat malignancies by controlling angiogenic activities; i.e., a humanized monoclonal antibody bevacizumab specifically targeting VEGF (vascular endothelial growth factor), as well as several tyrosine kinase inhibitors targeting VEGF-related pathways. It is obvious that VEGF is a key molecule for tumor neovascularization, however, strategies targeting VEGF may be a milestone and not a goal for antiangiogenic approach, because it has been elucidated the complexity of cancer microenvironments that mediate neovascularization and blood-borne metastasis. Specific subsets of chemoattractants recruit hematopoietic cells from the BM (bone marrow) that support tumor neovascularization in the primary lesion, and these mobilized cells are suggested to participate in pre-metastatic niche formation for circulating tumor cells. To establish safe and effective antiangiogenic therapies, it is important to understand the cross-communication between tumors and hosts that mediate proinflammatory milieu of both primary and metastatic lesions. This review discusses special features of tumor angiogenic vessels and their microenvironments, and in addition, recent topics including contribution of BM-derived cells, special mesenchymal cells and their chemoattractants that activate tumor vascular beds are summarized.