Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 188, Issue 5, Pages 1276-1288Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2018.01.016
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Funding
- Japan Society for the Promotion of Science [23890036]
- Italian Association for Cancer Research L' Associazione Italians per la Ricerca sul Cancro-Investigator Grant [15645]
- Swiss National Science Foundation [31003A-144206]
- Swiss Cancer League grant [OCS-02102-08-2007]
- Krebsliga Beider Basel grant [04-2010]
- Swiss National Science Foundation (SNF) [31003A_144206] Funding Source: Swiss National Science Foundation (SNF)
- Grants-in-Aid for Scientific Research [23890036, 17K15611] Funding Source: KAKEN
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Tumor invasion is a critical first step in the organismic dissemination of cancer cells and the formation of metastasis in distant organs, the most important prognostic factor and the actual cause of death in most of the cancer patients. We report herein that the cell surface protein podoplanin (PDPN), a potent inducer of cancer cell invasion, is conspicuously expressed by the invasive front of squamous cell carcinomas (SCCs) of the cervix in patients and in the transgenic human papillomavirus/estrogen mouse model of cervical cancer. Laser capture microscopy combined with gene expression profiling reveals that the expression of interferon-responsive genes is up-regulated in PDPN-expressing cells at the tumor invasive front, which are exposed to CD45-positive inflammatory cells. Indeed, PDPN expression can be induced in cultured SCC cell lines by single or combined treatments with interferon-gamma, transforming growth factor-beta, and/or tumor necrosis factor-alpha. Notably, shRNA-mediated ablation of either PDPN or STATE in A431 SCC cells repressed cancer cell invasion on s.c. transplantation into immunodeficient mice. The results highlight the induction of tumor cell invasion by the inflammatory cytoldne-stimulated expression of PDPN in the outermost cell Layers of cervical SCC.
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