Premium
CXCR7 expression correlates with tumor depth in cutaneous squamous cell carcinoma skin lesions and promotes tumor cell survival through ERK activation
Author(s) -
Hu Stephen ChuSung,
Yu HsinSu,
Yen FengLin,
Chen GwoShing,
Lan ChengChe E.
Publication year - 2014
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12557
Subject(s) - chemokine receptor , chemokine , cancer research , mapk/erk pathway , cxcr4 , biology , flow cytometry , receptor , cell , cell culture , cell growth , pathology , signal transduction , immunology , medicine , microbiology and biotechnology , biochemistry , genetics
The chemokine receptor CXCR7 has been demonstrated to be involved in the development of certain cancers, but its role in cutaneous squamous cell carcinoma (SCC) has not been previously investigated. We seek to determine whether CXCR7 is expressed in human cutaneous SCC skin lesions and SCC cell lines. In addition, we evaluate whether CXCR7 plays a role in SCC cell proliferation, survival and migration and which signalling pathways are involved. Using quantitative RT‐PCR to analyse the mRNA expression of 19 different chemokine receptors, we found that CXCR7 was much more highly expressed compared to other chemokine receptors in cutaneous SCC cell lines (HSC‐1 and HSC‐5). On immunohistochemical staining, CXCR7 was found to be expressed in 70% (28 of 40) of human cutaneous SCC tissue specimens, and its expression correlated with tumor depth >4 mm and cancer stage ≥II. CXCR7 but not CXCR4 protein was expressed on the surface of HSC‐1 and HSC‐5 cells by flow cytometry. Activation of the CXCR7 receptor by CXCL12 promoted survival of HSC‐1 and HSC‐5 cells through the ERK pathway, but had no significant effect on cell proliferation or migration. In summary, our findings indicate that CXCR7 is frequently expressed in cutaneous SCC skin lesions and its expression correlates with tumor depth and cancer stage. CXCR7 is the predominant chemokine receptor expressed in SCC cell lines, and activation of CXCR7 by CXCL12 promotes survival of SCC cells through the ERK pathway. These findings provide new insights into the significance of CXCR7 in the pathophysiology of SCC.