CD 47 is an adverse prognostic factor and a therapeutic target in gastric cancer

CD 47 is an antiphagocytic molecule that acts via ligation to signal regulatory protein alpha on phagocytes; its enhanced expression and therapeutic targeting have recently been reported for several malignancies. However, CD 47 expression in gastric cancer is not well documented. Immunohistochemical...

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Published in:Cancer medicine (Malden, MA) MA), 2015-09, Vol.4 (9), p.1322-1333
Main Authors: Yoshida, Kazumichi, Tsujimoto, Hironori, Matsumura, Kouji, Kinoshita, Manabu, Takahata, Risa, Matsumoto, Yusuke, Hiraki, Shuichi, Ono, Satoshi, Seki, Shuhji, Yamamoto, Junji, Hase, Kazuo
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Language:English
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Summary:CD 47 is an antiphagocytic molecule that acts via ligation to signal regulatory protein alpha on phagocytes; its enhanced expression and therapeutic targeting have recently been reported for several malignancies. However, CD 47 expression in gastric cancer is not well documented. Immunohistochemical expression of CD 47 in surgical specimens was investigated. Expression of CD 47 and CD 44, a known gastric cancer stem cell marker, were investigated in gastric cancer cell lines by flow cytometry. MKN 45 and MKN 74 gastric cancer cells were sorted by fluorescence‐activated cell sorting according to CD 44 and CD 47 expression levels, and their in vitro proliferation, spheroid‐forming capacity, and in vivo tumorigenicity were studied. In vitro phagocytosis of cancer cells by human macrophages in the presence of a CD 47 blocking monoclonal antibody (B6H12) and the survival of immunodeficient mice intraperitoneally engrafted with MKN 45 cells and B6H12 were compared to experiments using control antibodies. Immunohistochemistry of the clinical specimens indicated that CD 47 was positive in 57 out of 115 cases, and its positivity was an independent adverse prognostic factor. Approximately 90% of the MKN 45 and MKN 74 cells expressed CD 47 and CD 44. CD 47 hi gastric cancer cells showed significantly higher proliferation and spheroid colony formation than CD 47 lo , and CD 44 hi CD 47 hi cells showed the highest proliferation in vitro and tumorigenicity in vivo. B6H12 significantly enhanced in vitro phagocytosis of cancer cells by human macrophages and prolonged the survival of intraperitoneal cancer dissemination in mice compared to control antibodies. In conclusion, CD 47 is an adverse prognostic factor and promising therapeutic target in gastric cancer.
ISSN:2045-7634
2045-7634
DOI:10.1002/cam4.478