The tissue distribution and significance of B7-H4 in laryngeal carcinoma
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Lili Chen1,2, Meihua Jin1, Chunshi Li1,3, Yongjun Shang1,4 and Qinggao Zhang1
1Medical College, Dalian University, Dalian, People’s Republic of China
2Department of Clinical Laboratory, Laiwu City People Hospital, Laiwu, People’s Republic of China
3School of Pharmacy, Yanbian University, Yanji, People’s Republic of China
4Department of Orthopedics, Affiliated Hospital of Chifeng University, Chifeng, People’s Republic of China
Qinggao Zhang, email: firstname.lastname@example.org
Yongjun Shang, email: email@example.com
Keywords: B7-H4, laryngeal carcinoma, invasion and metastasis, EMT, STAT3
Received: January 23, 2017 Accepted: August 26, 2017 Published: September 21, 2017
The costimulatory signals CD28 and B7 have been shown to control tumor invasion and metastasis by regulating T cell activation, whereas the distribution characteristics of B7-associated proteins in laryngeal carcinoma (LC) tissue are still unclear. Here, the expression of members of the B7 superfamily, including B7-H1 (PD-L1), B7-DC (PD-L2) and B7-H4, in fifty-two LC samples was determined by immunohistochemistry, and the relationship between B7-H4 and epithelial-mesenchymal transition (EMT)-associated markers was further assessed by immunofluorescence double staining. Furthermore, the human LC cell lines, Hep-2 and TU212 cells, were further transfected to overexpress B7-H4, and cell invasion and metastasis were analyzed. The results showed that B7-H1, B7-DC and B7-H4 were expressed in the tumor cells, and their expression was restricted to the cell membrane and the cytoplasm. The positive rates of these molecules in the tumor tissues were 57.7% (30/52), 32.7% (17/52) and 34.6% (18/52), respectively. Interestingly, double immunofluorescence staining showed that B7-H4 is coexpression with EMT-related markers, including p-Smad2/3, Snail and Vimentin, in carcinoma cells. Moreover, overexpression of B7-H4 in Hep-2 cells promotes the expression of pSmad2/3 and Snail by activating AKT-STAT3 signaling. Transwell and wound-healing assays demonstrated that B7-H4 enhanced both Hep-2 and TU212 cell invasion and metastasis. Our results suggest that B7-H4 transmits feedback signaling to tumor cells and promotes invasion and metastasis by promoting EMT progression. Therefore, blocking B7-H4 signaling might be a novel treatment strategy for LC.
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