Human papillomavirus causes an angiogenic switch in keratinocytes which is sufficient to alter endothelial cell behavior

Journal Article · Wed Oct 10 04:00:00 EDT 2007 · Virology

DOI:https://doi.org/10.1016/j.virol.2007.05.030· OSTI ID:21077980

Chen, W ^[1]; Li, F; Mead, L; White, H ^[2]; Walker, J ^[1]; Ingram, D A ^[2]

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1. Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, 635 Barnhill Drive, Indianapolis, IN 46202-5120 (United States)
2. Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States)

One of the requirements for tumor growth is the ability to recruit a blood supply, a process known as angiogenesis. Angiogenesis begins early in the progression of cervical disease from mild to severe dysplasia and on to invasive cancer. We have previously reported that expression of human papillomavirus type 16 E6 and E7 (HPV16 E6E7) proteins in primary foreskin keratinocytes (HFKs) decreases expression of two inhibitors and increases expression of two angiogenic inducers [Toussaint-Smith, E., Donner, D.B., Roman, A., 2004. Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors. Oncogene 23, 2988-2995]. Here we report that HPV-induced early changes in the keratinocyte phenotype are sufficient to alter endothelial cell behavior both in vitro and in vivo. Conditioned media from HPV16 E6E7 expressing HFKs as well as from human cervical keratinocytes containing the intact HPV16 were able to stimulate proliferation and migration of human microvascular endothelial cells. In addition, introduction of the conditioned media into immunocompetent mice using a Matrigel plug model resulted in a clear angiogenic response. These novel data support the hypothesis that HPV proteins contribute not only to the uncontrolled keratinocyte growth seen following HPV infection but also to the angiogenic response needed for tumor formation.

• OSTI ID: 21077980
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 367; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BLOOD
CELL PROLIFERATION
GROWTH
IN VITRO
IN VIVO
MICE
NEOPLASMS
ONCOGENES
PHENOTYPE
PROTEINS