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      Keratinocytic Vascular Endothelial Growth Factor as a Novel Biomarker for Pathological Skin Condition

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          Abstract

          Skin is an emerging target tissue in pharmaceutical and cosmetic science. Safety assessment for dermal toxicity is a critical step for development of topically applicable pharmaceutical agents and ingredients in cosmetics. Urgent needs exist to set up toxicity testing methods for dermal safety, and identification of novel biomarkers for pathological cutaneous alteration is highly required. Here we will discuss if vascular endothelial growth factor (VEGF) has a potential as a biomarker for dermal impairment. Experimental and clinical evidences for induction of keratinocytic VEGF under pathological conditions will be reviewed.

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          Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis.

          Daniel Hicklin, Lee Ellis (2005)
          New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. Hence, the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research. The vascular endothelial growth factor (VEGF) pathway is well established as one of the key regulators of this process. The VEGF/VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities, cell-type expression, and function. Activation of the VEGF-receptor pathway triggers a network of signaling processes that promote endothelial cell growth, migration, and survival from pre-existing vasculature. In addition, VEGF mediates vessel permeability, and has been associated with malignant effusions. More recently, an important role for VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant sites of neovascularization. The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational design and development of agents that selectively target this pathway. Studies with various anti-VEGF/VEGF-receptor therapies have shown that these agents can potently inhibit angiogenesis and tumor growth in preclinical models. Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.
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            Vascular endothelial growth factor is a secreted angiogenic mitogen.

            David V. Goeddel, D Leung, N Ferrara … (1989)
            Vascular endothelial growth factor (VEGF) was purified from media conditioned by bovine pituitary folliculostellate cells (FC). VEGF is a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo. Complementary DNA clones for bovine and human VEGF were isolated from cDNA libraries prepared from FC and HL60 leukemia cells, respectively. These cDNAs encode hydrophilic proteins with sequences related to those of the A and B chains of platelet-derived growth factor. DNA sequencing suggests the existence of several molecular species of VEGF. VEGFs are secreted proteins, in contrast to other endothelial cell mitogens such as acidic or basic fibroblast growth factors and platelet-derived endothelial cell growth factor. Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF.
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              Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.

              James Dvorak, Paul V. Harvey, Harold Dvorak … (1983)
              Tumor ascites fluids from guinea pigs, hamsters, and mice contain activity that rapidly increases microvascular permeability. Similar activity is also secreted by these tumor cells and a variety of other tumor cell lines in vitro. The permeability-increasing activity purified from either the culture medium or ascites fluid of one tumor, the guinea pig line 10 hepatocarcinoma, is a 34,000- to 42,000-dalton protein distinct from other known permeability factors.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomol Ther (Seoul)
                Journal ID (iso-abbrev): Biomol Ther (Seoul)
                Journal ID (publisher-id): Biomol Ther (Seoul)
                Journal ID (publisher-id): ksp
                Title: Biomolecules & Therapeutics
                Publisher: The Korean Society of Applied Pharmacology
                ISSN (Print): 1976-9148
                ISSN (Electronic): 2005-4483
                Publication date (Print): January 2015
                Publication date (Electronic): 1 January 2015
                Volume: 23
                Issue: 1
                Pages: 12-18
                Affiliations
                [1 ]College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791
                [2 ]Collge of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742
                [3 ]College of Pharmacy, Chung-Ang University, Seoul 156-756
                [4 ]College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Republic of Korea
                Author notes
                [* ]Corresponding Author: E-mail: onbae@ 123456hanyang.ac.kr , Tel: +82-31-400-5805, Fax: +82-31-400-5958
                Article
                Publisher ID: bt-23-12
                DOI: 10.4062/biomolther.2014.102
                PMC ID: 4286744
                SO-VID: 771b06ba-0f60-4d32-ba9f-5b33fb5f7661
                Copyright © Copyright © 2015 The Korean Society of Applied Pharmacology
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 16 September 2014
                Date revision received : 01 October 2014
                Date accepted : 07 October 2014
                Categories
                Subject: Review

                Keywords: vascular endothelial growth factor (vegf),biomarker,keratinocytic damage,dermal toxicity
                Data availability:
                Keywords: vascular endothelial growth factor (vegf), biomarker, keratinocytic damage, dermal toxicity

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