TY - JOUR
T1 - Inflammatory Cytokines Induce Podoplanin Expression at the Tumor Invasive Front
AU - Kunita, Akiko
AU - Baeriswyl, Vanessa
AU - Meda, Claudia
AU - Cabuy, Erik
AU - Takeshita, Kimiko
AU - Giraudo, Enrico
AU - Wicki, Andreas
AU - Fukayama, Masashi
AU - Christofori, Gerhard
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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-γ, transforming growth factor-β, and/or tumor necrosis factor-α. Notably, shRNA-mediated ablation of either PDPN or STAT1 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 cytokine–stimulated expression of PDPN in the outermost cell layers of cervical SCC.
AB - 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-γ, transforming growth factor-β, and/or tumor necrosis factor-α. Notably, shRNA-mediated ablation of either PDPN or STAT1 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 cytokine–stimulated expression of PDPN in the outermost cell layers of cervical SCC.
UR - http://www.scopus.com/inward/record.url?scp=85045068465&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045068465&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2018.01.016
DO - 10.1016/j.ajpath.2018.01.016
M3 - Article
AN - SCOPUS:85045068465
VL - 188
SP - 1276
EP - 1288
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 5
ER -