PURPOSE: Head and neck squamous cell carcinomas (HNSCC) are characterized by high morbidity and mortality, largely due to the high invasive and metastatic potential of these tumors, high recurrence rates, and low treatment responses. Proteinases have been implicated in several aspects of tumor growth and metastasis in a broad range of tumors including HNSCC. EXPERIMENTAL DESIGN: Comprehensive expression profiling of proteinases [matrix metalloproteinases (MMPs), A disintegrin and metalloproteinase (ADAMs), and ADAMs with thrombospondin motif (ADAMTSs)] and their inhibitors [tissue inhibitor of metalloproteinases (TIMPs)] was done using quantitative real-time reverse transcription-PCR analysis of a large cohort of tissue samples representing the tumor (n = 83), the invasive margin (n = 41), and the adjacent tissue (n = 41) from 83 HNSCC patients, along with normal tissue controls (n = 13), as well as cell lines established from tumors of 34 HNSCC patients. RESULTS: The results show specifically elevated gene expression of several proteinases, including MMP1, MMP3, MMP10, and MMP13 within tumor tissue and peritumoral adjacent tissue. In addition, the results identify several novel HNSCC-associated proteinases, including ADAM8, ADAM9, ADAM17, ADAM28, ADAMTS1, ADAMTS8, and ADAMTS15. There were also significant differences in proteinase expression based on clinical parameters, i.e., tumor location, grade, and local invasion. MMP13 expression was significantly higher in large (>4 cm) locally invasive tumors (P < 0.05). MMP9 expression was significantly decreased in tumors with regional metastasis, whereas increased expression of ADAM8 was noted in the metastatic tumors (P < 0.001 for both). CONCLUSIONS: These findings suggest the HNSCC degradome as a valuable source of diagnostic, predictive, and prognostic molecular markers for these malignant tumors. Copyright 2010 AACR.
PURPOSE: Head and neck squamous cell carcinomas (HNSCC) are characterized by high morbidity and mortality, largely due to the high invasive and metastatic potential of these tumors, high recurrence rates, and low treatment responses. Proteinases have been implicated in several aspects of tumor growth and metastasis in a broad range of tumors including HNSCC. EXPERIMENTAL DESIGN: Comprehensive expression profiling of proteinases [matrix metalloproteinases (MMPs), A disintegrin and metalloproteinase (ADAMs), and ADAMs with thrombospondin motif (ADAMTSs)] and their inhibitors [tissue inhibitor of metalloproteinases (TIMPs)] was done using quantitative real-time reverse transcription-PCR analysis of a large cohort of tissue samples representing the tumor (n = 83), the invasive margin (n = 41), and the adjacent tissue (n = 41) from 83 HNSCC patients, along with normal tissue controls (n = 13), as well as cell lines established from tumors of 34 HNSCC patients. RESULTS: The results show specifically elevated gene expression of several proteinases, including MMP1, MMP3, MMP10, and MMP13 within tumor tissue and peritumoral adjacent tissue. In addition, the results identify several novel HNSCC-associated proteinases, including ADAM8, ADAM9, ADAM17, ADAM28, ADAMTS1, ADAMTS8, and ADAMTS15. There were also significant differences in proteinase expression based on clinical parameters, i.e., tumor location, grade, and local invasion. MMP13 expression was significantly higher in large (>4 cm) locally invasive tumors (P < 0.05). MMP9 expression was significantly decreased in tumors with regional metastasis, whereas increased expression of ADAM8 was noted in the metastatic tumors (P < 0.001 for both). CONCLUSIONS: These findings suggest the HNSCC degradome as a valuable source of diagnostic, predictive, and prognostic molecular markers for these malignant tumors. Copyright 2010 AACR.
Authors: Nijaguna B Prasad; Anne C Fischer; Alice Y Chuang; Jerry M Wright; Ting Yang; Hua-Ling Tsai; William H Westra; Nanette J Liegeois; Allan D Hess; Anthony P Tufaro Journal: Mod Pathol Date: 2013-12-20 Impact factor: 7.842
Authors: Wenyue Sun; Daria A Gaykalova; Michael F Ochs; Elizabeth Mambo; Demetri Arnaoutakis; Yan Liu; Myriam Loyo; Nishant Agrawal; Jason Howard; Ryan Li; Sun Ahn; Elana Fertig; David Sidransky; Jeffery Houghton; Kalyan Buddavarapu; Tiffany Sanford; Ashish Choudhary; Will Darden; Alex Adai; Gary Latham; Justin Bishop; Rajni Sharma; William H Westra; Patrick Hennessey; Christine H Chung; Joseph A Califano Journal: Cancer Res Date: 2013-12-18 Impact factor: 12.701
Authors: Ranee Mehra; Ilya G Serebriiskii; Roland L Dunbrack; Matthew K Robinson; Barbara Burtness; Erica A Golemis Journal: Drug Resist Updat Date: 2011-09-14 Impact factor: 18.500