Vascular Endothelial Growth Factor-D (VEGF-D): An Angiogenesis Bypass in Malignant Tumors

Abstract

Vascular endothelial growth factors (VEGFs) are the key regulators of vasculogenesis in normal and oncological development. VEGF-A is the most studied angiogenic factor secreted by malignant tumor cells under hypoxic and inflammatory stress, which made VEGF-A a rational target for anticancer therapy. However, inhibition of VEGF-A by monoclonal antibody drugs led to the upregulation of VEGF-D. VEGF-D was primarily described as a lymphangiogenic factor; however, VEGF-D’s blood angiogenic potential comparable to VEGF-A has already been demonstrated in glioblastoma and colorectal carcinoma. These findings suggested a role for VEGF-D in facilitating malignant tumor growth by bypassing the anti-VEGF-A antiangiogenic therapy. Owing to its high mitogenic ability, higher affinity for VEGFR-2, and higher expression in cancer, VEGF-D might even be a stronger angiogenic driver and, hence, a better therapeutic target than VEGF-A. In this review, we summarized the angiogenic role of VEGF-D in blood vasculogenesis and its targetability as an antiangiogenic therapy in cancer.

New insights into the role of the CHI3L2 protein in invasive ductal breast carcinoma: the CHI3L1 protein has a different role

“…Our hypothesis about the positive role of CHI3L2 in patient prognosis is noteworthy, especially considering that CHI3L1 plays a signi cant role as a poor prognostic factor in various cancers such as glioma and breast cancer [44]. Our previous study in IDC tumors [19] shows that CHI3L1 supports VEGFD-mediated angiogenesis in this type of cancer [45]. Hovewer in these studies, no signi cant correlations were found between CHI3L2 and angiogenesis markers even with CHI3L1, suggesting that CHI3L2 is not involved in angiogenesis in IDC and this similar protein: CHI3L1 and CHI3L2 appear to differ signi cantly in their function.…”

Green tea and hyaluronic acid gel enhance fibroblast activation and improves the gingival healing post-third molar extraction

“…Complimentarily, this study has shown also that challenged fibroblast with green tea and hyaluronic acid significantly over-expresses VEGF ( Vascular Endothelial Growth Factor; ~ 18 fold-changes). VEGF is one of the most significant factors during the entire angiogenesis 46 , 47 . From our point of view, challenged fibroblast creates a natural scaffold that is able to drive the regeneration steps, such as the angiogenesis.…”

A narrative review of the effects of vitamin D3 on orthodontic tooth movement: Focus on molecular and cellular mechanisms

“…The binding of VEGFs to their respective receptors, VEGFRs, triggers a cascade that enhances endothelial cell proliferation and motility, encourages the assembly of these cells into tubular structures, amplifies the permeability of blood vessels, and aids in sustaining the viability of vascular endothelial cells. These mechanisms are integral to angiogenesis (Bokhari & Hamar, 2023 ; Melincovici et al., 2018 ). The investigation by Nareswari et al.…”