Alternative Vascularization Mechanisms in Cancer

Abstract

Although cancer cells are not generally controlled by normal regulatory mechanisms, tumor growth is highly dependent on the supply of oxygen, nutrients, and host-derived regulators. It is now established that tumor vasculature is not necessarily derived from endothelial cell sprouting; instead, cancer tissue can acquire its vasculature by co-option of pre-existing vessels, intussusceptive microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis, or vasculogenic mimicry. The best-known molecular pathway driving tumor vascularization is the hypoxia-adaptation mechanism. However, a broad and diverse spectrum of genetic aberrations is associated with the development of the "angiogenic phenotype." Based on this knowledge, novel forms of antivascular modalities have been developed in the past decade. When applying these targeted therapies , the stage of tumor progression , the type of vascularization of the given cancer tissue , and the molecular machinery behind the vascularization process all need to be considered. A further challenge is finding the most appropriate combinations of antivascular therapies and standard radio-and chemotherapies. This review intends to integrate our recent knowledge in this field into a rational strategy that could be the basis for developing effective clinical modalities using antivascular therapy for cancer. (Am J

Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul

“…However, because VEGF is believed to be the most important among the molecules that participate in the regulation of EPCs, 14,18 one can assume that our observation on EPC numbers is the result of the reduced levels of this cytokine. Hence, we tested this hypothesis, but found normal VEGF levels in our patient population.…”

“…This cell population, endothelial progenitor cells (EPCs), appears to be involved in both the maintenance of vascular integrity 14 and postnatal vasculogenesis (for example, tumor vascularization). [15][16][17][18] Since their identification by Asahara et al, 19 several studies have shown reduced numbers and/or impaired function of EPCs in a variety of cardiovascular risk states, including diabetes mellitus, 20 hypercholesterolemia, 21 hypertension, 22 chronic renal failure, 23 rheumatoid arthritis 24 and cigarette smoking. 25 Alternatively, cardiovascular protective factors such as exercise training, 26 statin therapy, 27 angiotensin II receptor antagonists 28 and peroxisome proliferatoractivated receptor agonists 29 are known to increase EPC number and function.…”

A New Mechanism for Pillar Formation during Tumor-Induced Intussusceptive Angiogenesis: Inverse Sprouting

“…This can help tumors to develop resistance to anti-angiogenic treatments. 1,25 The main limitation of this study is the lack of direct in vivo evidence for collagen bundle movement. However, each of the available real-time imaging techniques has serious shortcomings/confounding factors that could hamper its use in studying in vivo pillar formation in tumorous conditions.…”

Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma

“…Both mechanisms occur in ischemic and tumor tissues in response to growth factors, mainly vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), produced by tumor and stromal cells (Folkman et al, 2001). However, it is now established that alternative vascularization mechanisms occur in tumors, that is, vascular co-option of preexisting vessels, intussusceptive microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis and vasculogenic mimicry (Dome et al, 2007).…”