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 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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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. |
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ISSN: | 2045-7634 2045-7634 |
DOI: | 10.1002/cam4.478 |