scholarly journals Multiple Roles for VEGF in Non-Melanoma Skin Cancer: Angiogenesis and Beyond

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Kelly E. Johnson ◽  
Traci A. Wilgus

Vascular endothelial growth factor (VEGF) is known to play a critical role in the development of non-melanoma skin cancers. VEGF is a potent pro-angiogenic factor and it is elevated in mouse and human skin tumors. The use of transgenic and knockout mice has shown that VEGF is essential for tumor development in multiple models of skin carcinogenesis and, until recently, the mechanism of action has been primarily attributed to the induction of angiogenesis. However, additional roles for VEGF have now been discovered. Keratinocytes can respond directly to VEGF, which could influence skin carcinogenesis by altering proliferation, survival, and stemness.In vivostudies have shown that loss of epidermal VEGFR-1 or neuropillin-1 inhibits carcinogenesis, indicating that VEGF can directly affect tumor cells. Additionally, VEGF has been shown to promote tumor growth by recruiting macrophages to skin tumors, which likely occurs through VEGFR-1. Overall, these new studies show that VEGF carries out functions beyond its well-established effects on angiogenesis and highlight the need to consider these alternative activities when developing new treatments for non-melanoma skin cancer.

Neoplasia ◽  
2015 ◽  
Vol 17 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Hyejun Ra ◽  
Emilio González-González ◽  
Md. Jashim Uddin ◽  
Bonnie L. King ◽  
Alex Lee ◽  
...  

2008 ◽  
Vol 24 (2) ◽  
pp. 72-75 ◽  
Author(s):  
Harry Moseley ◽  
Lorenzo Brancaleon ◽  
Andrea E. Lesar ◽  
James Ferguson ◽  
Sally H. Ibbotson

2021 ◽  
Vol 22 (13) ◽  
pp. 6736
Author(s):  
Josefa P. Alameda ◽  
Verónica A. García-García ◽  
Silvia López ◽  
Ana Hernando ◽  
Angustias Page ◽  
...  

Cylindromatosis (CYLD) is a deubiquitinase (DUB) enzyme that was initially characterized as a tumor suppressor of adnexal skin tumors in patients with CYLD syndrome. Later, it was also shown that the expression of functionally inactive mutated forms of CYLD promoted tumor development and progression of non-melanoma skin cancer (NMSC). However, the ability of wild-type CYLD to inhibit skin tumorigenesis in vivo in immunocompetent mice has not been proved. Herein, we generated transgenic mice that express the wild type form of CYLD under the control of the keratin 5 (K5) promoter (K5-CYLDwt mice) and analyzed the skin properties of these transgenic mice by WB and immunohistochemistry, studied the survival and proliferating characteristics of primary keratinocytes, and performed chemical skin carcinogenesis experiments. As a result, we found a reduced activation of the nuclear factor kappa B (NF-κB) pathway in the skin of K5-CYLDwt mice in response to tumor necrosis factor-α (TNF-α); accordingly, when subjected to insults, K5-CYLDwt keratinocytes are prone to apoptosis and are protected from excessive hyperproliferation. Skin carcinogenesis assays showed inhibition of tumor development in K5-CYLDwt mice. As a mechanism of this tumor suppressor activity, we found that a moderate increase in CYLD expression levels reduced NF-κB activation, which favored the differentiation of tumor epidermal cells and inhibited its proliferation; moreover, it decreased tumor angiogenesis and inflammation. Altogether, our results suggest that increased levels of CYLD may be useful for anti-skin cancer therapy.


2009 ◽  
Author(s):  
Narasimhan Rajaram ◽  
Dianne Kovacic ◽  
Michael F. Migden ◽  
Jason S. Reichenberg ◽  
Tri H. Nguyen ◽  
...  

2019 ◽  
Vol 100 ◽  
pp. 131-141 ◽  
Author(s):  
Ana Mara Ferreira Lima ◽  
Camila Ribeiro Daniel ◽  
Ricardo Scarparo Navarro ◽  
Benito Bodanese ◽  
Carlos Augusto Pasqualucci ◽  
...  

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