Angiogenic inhibition for the treatment of head and neck cancer.
Tumor angiogenesis is a fundamental step in tumor growth and proliferation. Fumagillin is an anti-angiogenic agent which is secreted by Aspergillus, but is also toxic. A fumagillin analogue, TNP-470, has been developed which is a potent angiogenic inhibitor with few side effects. TNP-470 has inhibited tumor growth in Lewis lung cancer and melanoma in animal models. This study was designed to test this proven anti-angiogenic agent's effects on head and neck cancer growth. Fort,v Harlan nude mice were injected subcutaneously with cancer cells from a human oral squamous cell carcinoma. After 3 weeks of tumor growth 25 mice were injected with TNP-470 subcutaneously at a distant site every other day for 30 days while 10 control mice received saline injections. Five mice began TNP-470 injections at the time of tumor injection to determine if TNP-470 can prevent tumor development. The tumor growth and development was unaffected by TNP-470 as compared to the control group. Therefore, the use of an angiogenic inhibitor had no effect on oral cancer growth. Analysis of the cell line utilized found abnormal mRNA expression, which included high p53 expression and low cyclin Dl expression. These results suggest that oral cancers are less dependent on angiogenesis than other tumor types. The genetic abnormalities may explain the angiogenesis independence that was demonstrated. Results found in other tumor types with angiogenic inhibitors cannot be extrapolated to oral cancer since genetic mutations may allow oral tumors to grow without neovascularization.
Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati Medical Center, Ohio, USA.
L L
LL
Gleich
N
N
Zimmerman
Y O
YO
Wang
J L
JL
Gluckman
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division; D019938:Cyclin D1 / Q000096:biosynthesis; D003510:Cyclohexanes; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012333:RNA, Messenger / Q000096:biosynthesis; D012717:Sesquiterpenes / Q000627:therapeutic use*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000970:Antineoplastic Agents; D003510:Cyclohexanes; D012333:RNA, Messenger; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D000077609:O-(Chloroacetylcarbamoyl)fumagillol