Neovascularization, Angiogenesis and Vasculogenic Mimicry in Cancer

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Background

Vasculature refers to the highly specialized system which serves to function in a number of physiological processes including tissue homeostasis. Formation of the vascular system occurs through vasculogenesis and angiogenesis; the de novo formation of vessels from endothelial stem cell progenitors, and the growth of new vessels from pre-existing vessels by sprouting, respectively. These highly complex events are mediated by the coordination of multiple cell types and signaling networks. Remarkably, these cellular events become deregulated in cancer cells leading to exacerbated angiogenesis, providing nutrients to tumors for sustainable growth. Pathological formation of new blood vessels confers advantages to tumor growth and metastasis. Therefore, the molecular mechanisms of angiogenesis are major issues in the understanding of cancer progression and constitute an important therapeutic target in human cancer.

Vasculogenic mimicry (VM) can be described as the perfusion of solid tumors through an independent route, or simultaneously with classical endothelial vessels. At a cellular level, this involves the de novo formation of patterned three dimensional (3D) vascular channel-like structures by tumor cells in combination with blood vessels (mosaic pattern). This differs from our traditional assumption that angiogenesis is the only means by which a tumor acquires a blood supply. These pseudo-3D channels contain plasma, erythrocytes and blood flow with a hemodynamics resembling angiogenesis. This suggests a potential explanation for evasive resistance to current anti-angiogenic therapies. VM has been described in many aggressive solid tumors including glioblastoma, breast, prostate, lung, hepatocellular and ovarian cancers, suggesting that it could be a novel hallmark of cancer. The presence of VM has been also associated with metastasis, poor clinical prognosis and low survival in cancer patients.
Certain proteins, signaling pathways, and non-coding RNAs have been reported to promote cell proliferation, migration, invasion, and matrix remodeling during angiogenesis and VM formation. A host of signaling molecules and their interaction with specific receptors are central to activating and modulating vessels and capillary-like structures. Importantly, hypoxia greatly promotes neovasculogenesis, angiogenesis, and VM formation, indicating that molecular mechanisms could be common across these cellular processes. However, the fine-tuning modulation and detailed crosstalk between signaling pathways remain to be completely elucidated.

Recent investigations have led to the identification of novel angiogenic targets and the development of promising anti-vascular agents. As novel therapies targeting angiogenesis and VM are needed for effective treatment of advanced cancer, studies highlighting the potential of novel molecular targets for therapies represent an attractive approach in cancer.

We welcome original research and review articles that cover recent advances made to understand the mechanisms of neovascularization, angiogenesis and vasculogenic mimicry, and a role of these processes in cancer initiation and progression. Studies devoted to the identification and characterization of novel potential biomarkers, therapeutic approaches targeting tumor vasculature and VM are especially welcomed. This collection will cover, but is not limited to, the following sub-topics:

1. Neovascularization from endothelial progenitors: mechanisms and regulation in normal and cancer cells
2. Cellular and molecular mechanisms of tumor angiogenesis in normal and cancer cells
3. Cellular and molecular mechanisms modulating vasculogenic mimicry in human malignancies
4. Regulatory roles of non-coding RNAs (lncRNAs, circRNAs, and miRNAs) in neovascularization, angiogenesis and vasculogenic mimicry.
5. Studies focused on the signaling pathways associated with angiogenesis and vasculogenic mimicry
6. Cellular 3D in vitro models for analysis of angiogenesis and vasculogenic mimicry as well as cancer cells interactions
7. Identification of novel potential therapeutic biomarkers targeting tumor vasculature and vasculogenic mimicry
8. Resistance mechanisms to anti-angiogenic therapies in cancer

The article types to be accepted include Original Research, Reviews, Mini-Reviews, Opinion, and Perspective pieces.

Keywords: Neovascularization, angiogenesis, vasculogenic mimicry, cancer, signaling pathways

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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