Angiogenesis-Based Dermatology by Jack L. Arbiser

Author:Jack L. Arbiser
Language: eng
Format: epub
Publisher: Springer London, London

VEGF is upregulated in melanoma, but is not expressed in normal melanocytes [24]. Increased expression of VEGF and VEGFRs in primary cutaneous melanoma as well as increased microvascular density strongly correlates with disease progression [25–27]. Serum VEGF levels are increased in melanoma patients compared with healthy controls [28].

The PDGF (Platelet-derived Growth Factor) Family

PDGF is a family of five growth factors (PDGF-AA, -AB, -BB, -CC, and -DD) that exert their biological effects through tyrosine kinase receptors, PDGFR-α and -β [21, 22]. The PDGF isoforms differ in their receptor specificity. The -A and -C chains bind only to PDGFR-α, and the -D chain binds only to PDGFR-β, whereas the -B chain binds to both. PDGFs together with angiopoietins and TGF-β have critical roles in endothelial cell-pericyte interaction [29]. During angiogenesis, endothelial cells produce PDGF-BB that stimulates PDGFR-β-expressing pericytes, and result in proliferation and migration of pericytes. Pericytes provide coverage of the vessel wall to stabilize the channels. Either PDGFR inhibition or pericyte deficiency leads to vessel leakage, tortuosity, and immature vessel formation. In the context of tumor angiogenesis, pericyte coverage of the vessel walls appears to be protective against metastasis as endothelial channels lined with pericytes limit tumor cell intravasation as opposed to those that are loosely assembled and leaky [30].

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