Bone marrow plasma cells and stromal cells in multiple myeloma (MM) have been shown to be capable of releasing cytokines with angiogenic properties. Plasma cells can also express adhesion molecules ...controlling their adhesive interactions with endothelial cells. In the present study, we have evaluated by immunohistochemistry the extent of angiogenesis in the bone marrow of: a) 51 patients with active and non-active MM; b) 25 patients with monoclonal gammopathy of undetermined significance (MGUS). Plasma cells were investigated by flow cytometry for the expression of the adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. The results showed that, while angiogenesis was very low or absent in patients with MGUS and non-active MM, it increased markedly in those with active MM. The highest detectability of plasma cell adhesion molecules, except LAM-1, was also found in these patients. The functional significance of these findings is unknown. Their consistent occurrence in the bone marrow of active myeloma patients, however, strongly suggests that more frequent adhesive interactions between plasma cells and their microvasculature underlie tumor dissemination.
Angiogenesis is an important pathway in tumour growth and progression. Overexpression of pro-angiogenic factor or down regulation of physiologic angiogenic inhibitors are the stimuli that induce new ...blood vessel formation from a pre-existing vascular bed. On the other hand tumour vasculature is a major important factor influencing the therapeutic application of hyperthermia used as anticancer therapy. Both endothelial cells and microvessels can be lethally damaged by the hyperthermia. Because tumour vasculature is a target of hyperthermia combined treatments with angiogenesis inhibiting agents or vascular disrupting agents and hyperthermia may lead to synergetic effects or potentiation of the combined therapy over each modality alone. In this chapter we summarize the state of the art regarding the combination between drugs that targeting tumour vasculature and hyperthermia, furthermore the pre-clinical rationale for future clinical trials is suggested.
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