Lyn Expression in Osteoblastic Osteosarcoma Tissues and Its Correlation with Clinicopathologic Factors
1
조회
0
다운로드
0
인용
0
참고문헌
초록
Background : The Src family kinases (SFKs) are involved in multiple aspects of tumorigenesis, such as, proliferation, migration, and angiogenesis, and are involved in the generation and progression of many types of tumors. Furthermore, dasatinib, a general SFKs inhibitor was recently approved for use in chronic myeloid leukemia. This study was performed to evaluate the expression of Lyn, a member of the SFKs, in osteosarcoma tissues. Methods : One hundred and sixteen patients with osteoblastic osteosarcoma were selected for Lyn expression analysis. The correlation between Lyn expression in tumor sections and patients’ clinicopathologic characteristics and the prognostic significance of Lyn expression were evaluated. Results : Lyn was found to be expressed in 52 of the 116 patients (44.8%), and Lyn positive tumor was found to be significantly associated with a lytic tumor pattern on plain radiographs (p = 0.04). Furthermore, those positive for Lyn showed longer metastasis free survival (5-year metastasis free survival, 65.2% for Lyn positive and 46.8% for Lyn negative; p = 0.06), though this was only marginally significant. Conclusions : Lyn was found to be overexpressed in osteosarcoma tissues, and this overexpression was found to be correlated with osteolysis.
Abstract
Background : The Src family kinases (SFKs) are involved in multiple aspects of tumorigenesis, such as, proliferation, migration, and angiogenesis, and are involved in the generation and progression of many types of tumors. Furthermore, dasatinib, a general SFKs inhibitor was recently approved for use in chronic myeloid leukemia. This study was performed to evaluate the expression of Lyn, a member of the SFKs, in osteosarcoma tissues. Methods : One hundred and sixteen patients with osteoblastic osteosarcoma were selected for Lyn expression analysis. The correlation between Lyn expression in tumor sections and patients’ clinicopathologic characteristics and the prognostic significance of Lyn expression were evaluated. Results : Lyn was found to be expressed in 52 of the 116 patients (44.8%), and Lyn positive tumor was found to be significantly associated with a lytic tumor pattern on plain radiographs (p = 0.04). Furthermore, those positive for Lyn showed longer metastasis free survival (5-year metastasis free survival, 65.2% for Lyn positive and 46.8% for Lyn negative; p = 0.06), though this was only marginally significant. Conclusions : Lyn was found to be overexpressed in osteosarcoma tissues, and this overexpression was found to be correlated with osteolysis.
참고문헌 (28)
- Link MP, "Osteosarcoma. In: Principles and practice of pediatric oncology. 5th ed", pp.1074~1115 (2005), Lippincott Williams & Wilkins
- Rucci N, "Inhibition of protein kinase c-Src as a therapeutic approach for cancer and bone metastases", Anticancer Agents Med Chem, 8, pp.342~349 (2008)
- Guan H, "Targeting Lyn inhibits tumor growth and metastasis in Ewing’s sarcoma", Mol Cancer Ther, 7, pp.1807~1816 (2008)
- Allgayer H, "Transcriptional induction of the urokinase receptor gene by a constitutively active Src.Requirement of an upstream motif(-152", -135)bound with Sp1, 1999, pp.274, 18428~18437
- Windham TC, "Src activation regulates anoikis in human colon tumor cell lines", Oncogene, 21, pp.7797~7807 (2002)
- Lau GM, "Expression of Src and FAK in hepatocellular carcinoma and the effect of Src inhibitors on hepatocellular carcinoma in vitro", Dig Dis Sci, 54, pp.1465~1474 (2009)
- Masaki T, "pp60c-src activation in hepatocellular carcinoma of humans and LEC rats", Hepatology, 27, pp.1257~1264 (1998)
- Ito Y, "Activation of c-Src gene product in hepatocellular carcinoma is highly correlated with the indices of early stage phenotype", J Hepatol, 35, pp.68~73 (2001)
- Lombardo LJ, "Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methy lpyrimidin-4-ylamino)thiazole-5-carboxamide(BMS-354825),a dual Src", Abl kinase inhibitor with potent antitumor activity in preclinical assays, 2004, pp.47, 6658~6661
- Tsao AS, "Activated Src kinase is expressed in malignant pleural mesothelioma tumors; dasatinib inhibition leads to cytotoxicity, cell cycle inhibition and prevention of invasion and migration", 2007 American Society of Clinical Oncology Annual Meeting, Chicago, IL. Abstract No. 7713 (2007)
- Talpaz M, "Dasatinib in imatinib-resistant Philadelphia chromosome-positive leuke mias", N Engl J Med, 354, pp.2531~2541 (2006)
- Giaccone G, "Src as a potential therapeutic target in nonsmall-cell lung cancer", Ann Oncol, 19, pp.1219~1223 (2008)
- Roginskaya V, "Therapeutic targeting of Src-kinase Lyn in myeloid leukemic cell growth", Leukemia, 13, pp.855~861 (1999)
- Goldenberg-Furmanov M, "Lyn is a target gene for prostate cancer:sequence-based inhibition induces regression of human tumor xenografts", Cancer Res, 64, pp.1058~1066 (2004)
- Bates RC, "A CD44 survival pathway triggers chemoresistance via lyn kinase and phosphoinositide 3-kinase", Akt in colon carcinoma cells, 2001, pp.61, 5275~5283
- Fu Y, "CHK negatively regulates Lyn kinase and suppresses pancreatic cancer cell invasion", Int J Oncol, 29, pp.1453~1458 (2006)
- Huang F, "Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib:rationale for patient selection", Cancer Res, 67, pp.2226~2238 (2007)
- Shor AC, "Dasatinib inhibits migration and invasion in diverse human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on SRC kinase for survival", Cancer Res, 67, pp.2800~2808 (2007)
- Meyers PA, "Chemotherapy for nonmetastatic osteogenic sarcoma:the Memorial Sloan-Kettering experience", J Clin Oncol, 10, pp.5~15 (1992)
- Sakai T, "An epitope localized in c-Src negative regulatory domain is a potential marker in early stage of colonic neoplasms", Lab Invest, 78, pp.219~225 (1998)
- Tsao AS, "Inhibition of c-Src expression and activation in malignant pleural mesothelioma tissues leads to apoptosis,cell cycle arrest,and decreased migration and invasion", Mol Cancer Ther, 6, pp.1962~1972 (2007)
- Stettner MR, "Lyn kinase activity is the predominant cellular SRC kinase activity in glioblastoma tumor cells", Cancer Res, 65, pp.5535~5543 (2005)
- Metcalf CA 3rd, "Targeting protein kinases for bone disease:discovery and development of Src inhibitors", Curr Pharm Des, 8, pp.2049~2075 (2002)
- Miyazaki T, "Regulation of cytochrome c oxidase activity by c-Src in osteoclasts", J Cell Biol, 160, pp.709~718 (2003)
- Soriano P, "Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice", Cell, 64, pp.693~702 (1991)
- Edwards JC, "c-Src control of chloride channel support for osteoclast HCl transport and bone resorption", J Biol Chem, 281, pp.28011~28022 (2006)
- Kaabeche K, "Cblmediated degradation of Lyn and Fyn induced by constitutive fibroblast growth factor receptor-2 activation supports osteoblast differentiation", J Biol Chem, 279, pp.36259~36267 (2004)
- Iravani S, "Elevated c-Src protein expression is an early event in colonic neoplasia", Lab Invest, 78, pp.365~371 (1998)