期刊
LARYNGOSCOPE
卷 122, 期 1, 页码 95-102出版社
WILEY
DOI: 10.1002/lary.22345
关键词
Bone morphogenetic protein; oral cancer; squamous cell carcinoma; Level of Evidence: 5
资金
- National Institute of Dental and Craniofacial Research/National Institutes of Health (NIDCR/NIH) [DE017137-01A1]
- Bernard Hemann family
Objectives/Hypothesis: To establish the relevance of the bone morphogenetic protein (BMP) signaling pathway in human oral squamous cell carcinoma (OSCCA) cell lines and determine if there is a biologic impact of stimulating this pathway with recombinant human (rh) BMP-2. Study Design: In vitro laboratory investigations and in vivo analysis using an orthotopic animal model for oral cancer. Methods: Gene expression profiles for BMP-2 and components of the BMP-signaling pathway were determined using reverse transcriptase-polymerase chain reaction. In vivo effects were evaluated using Kaplan-Meier survival analysis and studying histopathologic changes in established tumor xenografts with or without rhBMP-2 pretreatment. A phosphokinase array was used to detect levels of activation in signaling kinases. Results: The BMP-2 gene was expressed in 90% of the 30 OSCCA cell lines tested. Gene expression of all components of the BMP-signaling pathway was highly conserved. Tumor xenografts established with rhBMP-2-treated cells showed more rapid local growth that resulted in worse animal survival as compared to the control group. These tumors had a more poorly differentiated morphology. Changes in protein kinases suggested interactions of BMP-2 signaling with the Wnt-beta-catenin, and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. Conclusions: Human OSCCA cell lines frequently express BMP-2 and all necessary components of the BMP-signaling pathway. Exogenous treatment of human OSCCA cell lines with rhBMP-2 prior to engraftment in an orthotopic animal model caused the subsequent tumors to be more locally aggressive with worse survival. Continued caution should be used for considering rhBMP-2 for reconstruction of bone defects in oral cancer patients.
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