Unimpeded skin carcinogenesis in K14-HPV16 transgenic mice deficient for plasminogen activator inhibitor

Anne Masset, Catherine Maillard, Nor Eddine Sounni, Nathalie Jacobs, Françoise Bruyére, Philippe Delvenne, Marlene Tacke, Thomas Reinheckel, Jean Michel Foidart, Lisa M. Coussens, Agnès Noaël

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Angiogenesis, extracellular matrix remodeling and cell migration are associated with cancer progression and involve at least, the plasminogen activating system and its main physiological inhibitor, the plasminogen activator inhibitor-1 (PAI-1). Considering the recognized importance of PAI-1 in the regulation of tumor angiogenesis and invasion in murine models of skin tumor transplantation, we explored the functional significance of PAI-1 during early stages of neoplastic progression in the transgenic mouse model of multistage epithelial carcinogenesis (K14-HPV16 mice). We have studied the effect of genetic deletion of PAI-1 on inflammation, angiogenesis, lymphangiogenesis and tumor progression. In this model, PAI-1 deficiency neither impaired keratinocyte hyperproliferation or tumor development nor affected the infiltration of inflammatory cells and development of angiogenic or lymphangiogenic vasculature. We are reporting evidence for concomitant lymphangiogenic and angiogenic switches independent to PAI-1 status. Taken together, these data indicate that PAI-1 is not rate limiting for neoplastic progression and vascularization during premalignant progression, or that there is a functional redundancy between PAI-1 and other tumor regulators, masking the effect of PAI-1 deficiency in this long-term model of multistage epithelial carcinogenesis.

Original languageEnglish (US)
Pages (from-to)283-293
Number of pages11
JournalInternational Journal of Cancer
Volume128
Issue number2
DOIs
StatePublished - Jan 15 2011

Keywords

  • K14-HPV16
  • angiogenesis
  • lymphangiogenesis
  • plasminogen activator

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Masset, A., Maillard, C., Sounni, N. E., Jacobs, N., Bruyére, F., Delvenne, P., Tacke, M., Reinheckel, T., Foidart, J. M., Coussens, L. M., & Noaël, A. (2011). Unimpeded skin carcinogenesis in K14-HPV16 transgenic mice deficient for plasminogen activator inhibitor. International Journal of Cancer, 128(2), 283-293. https://doi.org/10.1002/ijc.25326