EMMPRIN expression is required for response to bevacizumab therapy in HNSCC xenografts.
The HNSCC cell line, FaDu was stably transfected with control vector (FaDu) or with plasmid expressing small interfering RNA against EMMPRIN (FaDu/siE). Tumor cells were treated with bevacizumab (0, 25, 50, and 75 ng/ml) in vitro, and then cell counts were performed at 72 h. For in vivo analysis, tumor cells were xenografted onto the flank of SCID mice, and were treated with 100 microg bevacizumab twice weekly for three weeks. Xenograft samples from the control and treatment groups were analyzed for microvessel density. Escalating doses of bevacizumab had no effect on the growth of tumor cells in vitro (P.or=0.086). However, tumor xenografts expressing EMMPRIN responded to bevacizumab treatment (P=0.0013), whereas the EMMPRIN knockdown cell line did not (P=0.7942). Immunohistochemical analysis demonstrated that microvascular density was reduced in the treated FaDu tumors (P=0.005), but not in the FaDu/siE tumors (P=0.48). Currently there is limited information on biomarkers to predict response to bevacizumab. By demonstrating effectiveness of bevacizumab therapy in tumors that express EMMPRIN, but not in tumors with silenced EMMPRIN expression, this study suggests that EMMPRIN may serve as a biomarker for response to bevacizumab treatment.
Newman
J Robert
JR
Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, University of Alabama at Birmingham, BDB Suit 563, 1808 7th Avenue South, Birmingham, AL 358294-0012, USA.
Helman
Emily E
EE
Safavy
Seena
S
Zhang
Wenyue
W
Rosenthal
Eben L
EL
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001483:Base Sequence; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D000068258:Bevacizumab; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers; D020868:Gene Silencing; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D014183:Transplantation, Heterologous
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C497886:BSG protein, human; D017931:DNA Primers; D051926:Basigin; D000068258:Bevacizumab