Endothelial progenitor cells in multiple myeloma neovascularization: a brick to the wall

Abstract

Multiple myeloma (MM) is characterized by the clonal expansion of plasma cells in the bone marrow that leads to events such as bone destruction, anaemia and renal failure. Despite the several therapeutic options available, there is still no effective cure, and the standard survival is up to 4 years. The evolution from the asymptomatic stage of monoclonal gammopathy of undetermined significance to MM and the progression of the disease itself are related to cellular and molecular alterations in the bone marrow microenvironment, including the development of the vasculature. Post-natal vasculogenesis is characterized by the recruitment to the tumour vasculature of bone marrow progenitors, known as endothelial progenitor cells (EPCs), which incorporate newly forming blood vessels and differentiate into endothelial cells. Several processes related to EPCs, such as recruitment, mobilization, adhesion and differentiation, are tightly controlled by cells and molecules in the bone marrow microenvironment. In this review, the bone marrow microenvironment and the mechanisms associated to the development of the neovasculature promoted by EPCs are discussed in detail in both a non-pathological scenario and in MM. The latest developments in therapy targeting the vasculature and EPCs in MM are also highlighted. The identification and characterization of the pathways relevant to the complex setting of MM are of utter importance to identify not only biomarkers for an early diagnosis and disease progression monitoring, but also to reveal intervention targets for more effective therapy directed to cancer cells and the endothelial mediators relevant to neovasculature development.

Bone Marrow Stromal Cells-Induced Drug Resistance in Multiple Myeloma

“…The expression of CD133 on a subset of BM endothelial cells during the active phase of the disease is indicative of the recruitment of CD133+ progenitor cells, derived from a common progenitor namely hemangioblast, which contributes to the neovascularization by means of the reactivation of the ancestral phenomenon named "vasculogenesis" [23][24][25][26][27].…”

Angiogenesis and Antiangiogenesis in Multiple Myeloma

“…It enhances vascular permeability, facilitates plasma extravasation, increases interstitial pressure, induces hypoxia, and upregulates hypoxia-inducible factor-1 alpha (HIF-1α) and VEGF [39]. Some MM endothelial cells express the CD133 indicating their derivation from a subset of CD133+ progenitor cells which contribute to the formation of blood neovessels [26,40,41]. MM plasma cells recruit BM and circulating CD133+ progenitor cells into the tumor microenvironment by mean the release of a high quantity of VEGF, FGF-2, and IGF [26].…”

“…Various studies have demonstrated that endothelial progenitor cells (EPCs) can be isolated from patients with MM [40,[66][67][68][69] and contribute to the formation of new blood vessels [40]. Moreover, circulating EPCs expressing CD146+, CD105+, and CD34+ are increased in MM patients compared to healthy controls [66,67].…”

MicroRNA-126 is a prospective target for vascular disease

“…Under high glucose condition associated with ECs dysfunction, decreasing miR-126 could increase SDF-1 expression, and also directly increased progenitor cells migration and adhesion [11,12] , and further improve stroke outcome by differentiating into endothelial cells or through the paracrine effects. Tenreiro et al [13] demonstrated endothelial cells improved ischemic recovery by differentiation into ECs. Chen et al [14] demonstrated progenitor cells secreted IL-8 to promote angiogenesis during ischemia.…”