Clinical and biological significance of tissue transglutaminase in ovarian carcinoma.
Enviado por Pablo Vivas-Mejia el
Título | Clinical and biological significance of tissue transglutaminase in ovarian carcinoma. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Autores | Hwang, JYoung, Mangala, LS, Fok, JY, Lin, YG, Merritt, WM, Spannuth, WA, Nick, AM, Fiterman, DJ, Vivas-Mejia, P, Deavers, MT, Coleman, RL, Lopez-Berestein, G, Mehta, K, Sood, AK |
Journal | Cancer Res |
Volume | 68 |
Issue | 14 |
Pagination | 5849-58 |
Date Published | 2008 Jul 15 |
ISSN | 1538-7445 |
Palabras clave | Animals, Antineoplastic Agents, Carcinoma, Cell Line, Tumor, Disease Progression, Female, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Gene Silencing, Humans, Mice, Mutation, Neoplasm Transplantation, Ovarian Neoplasms, Transglutaminases |
Abstract | Tissue type transglutaminase (TG2) is a unique multifunctional protein that plays a role in many steps in the cancer metastatic cascade. Here, we examined the clinical (n = 93 epithelial ovarian cancers) and biological (in vitro adhesion, invasion, and survival and in vivo therapeutic targeting) significance of TG2 in ovarian cancer. The overexpression of TG2 was associated with significantly worse overall patient survival in both univariate and multivariate analyses. Transfection of TG2 into SKOV3ip1 cells promoted attachment and spreading on fibronectin-coated surfaces and increased the in vitro invasive potential of these cells. Conversely, TG2 silencing with small interfering RNA (siRNA) of HeyA8 cells significantly decreased the invasive potential of the cells and also increased docetaxel-induced cell death. In vivo therapy experiments using chemotherapy-sensitive (HeyA8) and chemotherapy-resistant (HeyA8-MDR and RMG2) models showed significant antitumor activity both with TG2 siRNA-1,2-dioleoyl-sn-glycero-3-phosphatidylcholine alone and in combination with docetaxel chemotherapy. This antitumor activity was related to decreased proliferation and angiogenesis and increased tumor cell apoptosis in vivo. Taken together, these findings indicate that TG2 overexpression is an adverse prognostic factor in ovarian carcinoma and TG2 targeting may be an attractive therapeutic approach. |
DOI | 10.1158/0008-5472.CAN-07-6130 |
Alternate Journal | Cancer Res. |
PubMed ID | 18632639 |
PubMed Central ID | PMC2547344 |
Grant List | CA092115 / CA / NCI NIH HHS / United States CA109298 / CA / NCI NIH HHS / United States CA110793 / CA / NCI NIH HHS / United States P50 CA083639 / CA / NCI NIH HHS / United States P50 CA083639-06A1 / CA / NCI NIH HHS / United States P50CA083639 / CA / NCI NIH HHS / United States R01 CA109298 / CA / NCI NIH HHS / United States R01 CA109298-03 / CA / NCI NIH HHS / United States R01 CA110793 / CA / NCI NIH HHS / United States R01 CA110793-03 / CA / NCI NIH HHS / United States |