دورية أكاديمية
أعرض في EDS

Functional significance of VEGFR-2 on ovarian cancer cells.

التفاصيل البيبلوغرافية
العنوان: Functional significance of VEGFR-2 on ovarian cancer cells.
المؤلفون: Spannuth WA; Department of Gynecologic Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA., Nick AM, Jennings NB, Armaiz-Pena GN, Mangala LS, Danes CG, Lin YG, Merritt WM, Thaker PH, Kamat AA, Han LY, Tonra JR, Coleman RL, Ellis LM, Sood AK
المصدر: International journal of cancer [Int J Cancer] 2009 Mar 01; Vol. 124 (5), pp. 1045-53.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 1995- : New York, NY : Wiley-Liss
Original Publication: 1966-1984 : Genève : International Union Against Cancer
مواضيع طبية MeSH: Ovarian Neoplasms/*pathology , Vascular Endothelial Growth Factor Receptor-2/*physiology, Animals ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Apoptosis ; Cell Proliferation ; Crk-Associated Substrate Protein/physiology ; Female ; Humans ; Mice ; Ovarian Neoplasms/blood supply ; Ovarian Neoplasms/therapy ; Signal Transduction ; Vascular Endothelial Growth Factor Receptor-2/analysis ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors ; Xenograft Model Antitumor Assays
مستخلص: Vascular endothelial growth factor receptor (VEGFR) has recently been discovered on ovarian cancer cells, but its functional significance is unknown and is the focus of this study. By protein analysis, A2780-par and HeyA8 ovarian cancer cell lines expressed VEGFR-1 and HeyA8 A2774, and SKOV3ip1 expressed VEGFR-2. By in situ hybridization (ISH), 85% of human ovarian cancer specimens showed moderate to high VEGFR-2 expression, whereas only 15% showed moderate to high VEGFR-1 expression. By immunofluorescence, little or no VEGFR-2 was detected in normal ovarian surface epithelial cells, whereas expression was detected in 75% of invasive ovarian cancer specimens. To differentiate between the effects of tumor versus host expression of VEGFR, nude mice were injected with SKOV3ip1 cells and treated with either human VEGFR-2 specific antibody (1121B), murine VEGFR-2 specific antibody (DC101) or the combination. Treatment with 1121B reduced SKOV3ip1 cell migration by 68% (p < 0.01) and invasion by 72% (p < 0.01), but exposure to VEGFR-1 antibody had no effect. Treatment with 1121B effectively blocked VEGF-induced phosphorylation of p130Cas. In vivo treatment with either DC101 or 1121B significantly reduced tumor growth alone and in combination in the SKOV3ip1 and A2774 models. Decreased tumor burden after treatment with DC101 or 1121B correlated with increased tumor cell apoptosis, decreased proliferative index, and decreased microvessel density. These effects were significantly greater in the combination group (p < 0.001). We show functionally active VEGFR-2 is present on most ovarian cancer cells. The observed anti-tumor activity of VEGF-targeted therapies may be mediated by both anti-angiogenic and direct anti-tumor effects.
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معلومات مُعتمدة: R01 CA110793-05 United States CA NCI NIH HHS; R01 CA110793 United States CA NCI NIH HHS; CA110793 United States CA NCI NIH HHS; P50 CA083639 United States CA NCI NIH HHS; P50CA083639 United States CA NCI NIH HHS; T32 CA101642 United States CA NCI NIH HHS; CA109298 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Antibodies, Monoclonal)
0 (Crk-Associated Substrate Protein)
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
تواريخ الأحداث: Date Created: 20081206 Date Completed: 20090123 Latest Revision: 20211020
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC2668132
DOI: 10.1002/ijc.24028
PMID: 19058181
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-0215
DOI:10.1002/ijc.24028