antiangiogenic therapy

Basic mechanisms of angiogenesis in hematological malignancies

REVIEWS , , ,

А.А. Vartanyan

N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

Currently, the concept of VEGF-induced angiogenesis as a growth-limiting factor for solid tumors is generally accepted. Growing evidence indicates that the angiogenic growth factors also play an important role in the development and persistence of hematological malignancies. Neoplastic cells induce angiogenesis within the bone marrow through the secretion of soluble angiogenesis activators. VEGF is thought to be a major angiogenic factor involved in bone marrow vascularization. On the other hand, the increased VEGF secretion leads to the release of several soluble cytokines such as GM-CSF, G-CSF, IL-6, PlGF, HGF, IGF, and angiopoietins by the bone marrow microenvironment cells that promote survival and proliferation of malignant cells. The increased plasma VEGF level in the patients with hematological malignancies is considered the most important prognostic factor indicating an unfavorable outcome.

In this review, we discuss the autocrine and paracrine mechanisms of VEGF accumulation in the bone marrow, as well as the angiogenesis-related and -unrelated effects of VEGF. In conclusion, the potential of VEGF signaling inhibition in various hematological malignancies for therapy and its outcomes is discussed.

Keywords: oncohematology, bone marrow, angiogenesis, antiangiogenic therapy.

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