Vascular endothelial growth factor expression in early stage ovarian carcinoma

Paley, Pamela J.; Staskus, Katherine; Gebhard, B.; Mohanraj, D.; Twiggs, Leo B.; Carson, Linda F.; Ramakrishnan, Sundaram

doi:10.1002/(sici)1097-0142(19970701)80:1<98::aid-cncr13>3.0.co;2-a

Cited by 332 publications

(201 citation statements)

References 20 publications

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“…VEGF is the prototype of the VEGF family, and its proangiogenic signals are mainly transmitted via its type 2 receptor (VEGFR2) on endothelial cells (5). High levels of VEGF have been found in ovarian cancers, which is associated with poor survival of patients in both early and advanced stages of the disease (6,7). In animal models of ovarian cancer, inhibition of VEGF reduces tumor growth and inhibits ascites accumulation (8).…”

Section: Introductionmentioning

confidence: 99%

Vasohibin-2 Expressed in Human Serous Ovarian Adenocarcinoma Accelerates Tumor Growth by Promoting Angiogenesis

Takahashi

Koyanagi

Suzuki

et al. 2012

Molecular Cancer Research

106

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Vasohibin-1 (VASH1) is a VEGF-inducible endothelium-derived angiogenesis inhibitor and VASH2 is its homolog. Our previous analysis revealed that VASH1 is expressed in endothelial cells to terminate angiogenesis, whereas VASH2 is expressed in infiltrating mononuclear cells mobilized from bone marrow to promote angiogenesis in a mouse model of hypoxia-induced subcutaneous angiogenesis. To test the possible involvement of VASH2 in the tumor, we examined human ovarian cancer cells for the presence of VASH2. Immunohistochemical analysis revealed that VASH2 protein was preferentially detected in cancer cells of serous ovarian adenocarcinoma. We then used SKOV-3 and DISS, two representative human serous adenocarcinoma cell lines, and examined the role of VASH2 in the tumor. The knockdown of VASH2 showed little effect on the proliferation of cancer cells in vitro but notably inhibited tumor growth, peritoneal dissemination, and tumor angiogenesis in a murine xenograft model. Next, we stably transfected the human VASH2 gene into two types of murine tumor cells, EL-4 and MLTC-1, in which endogenous VASH2 was absent. When either EL-4 or MLTC-1 cells were inoculated into VASH2 (À/À) mice, the VASH2 transfectants formed bigger tumors when compared with the controls, and the tumor microvessel density was significantly increased. VASH2 stimulated the migration of endothelial cells, and its increased expression in cancer cells is related to the decrease of mir-200b. These results indicate that VASH2 expressed in serous ovarian carcinoma cells promoted tumor growth and peritoneal dissemination by promoting angiogenesis. Mol Cancer Res; 10(9); 1135-46. Ó2012 AACR.

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Section: Introductionmentioning

confidence: 99%

Vasohibin-2 Expressed in Human Serous Ovarian Adenocarcinoma Accelerates Tumor Growth by Promoting Angiogenesis

Takahashi

Koyanagi

Suzuki

et al. 2012

Molecular Cancer Research

106

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“…Many studies have shown that increased VEGF expression correlates with poor prognosis in ovarian cancer patients (1)(2)(3). VEGF is expressed by ovarian cancer cells (4) and is found at high levels in the malignant ascites of humans as well as in animal models (5-7).…”

mentioning

confidence: 99%

Vascular Endothelial Growth Factor Transcriptional Activation Is Mediated by Hypoxia-inducible Factor 1α, HDM2, and p70S6K1 in Response to Phosphatidylinositol 3-Kinase/AKT Signaling

Skinner

Zheng

Fang

et al. 2004

Journal of Biological Chemistry

186

147

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Vascular endothelial growth factor (VEGF) expression is elevated in ovarian and other cancer cells. However, the mechanism that causes the increase in VEGF expression still remains to be elucidated. In this study, we demonstrated that activation of PI3K signaling mediated VEGF protein expression at the transcriptional level through hypoxia-inducible factor 1␣ (HIF-1␣) expression in human ovarian cancer cells. We found that inhibition of PI3K activity by LY294002 decreased VEGF transcriptional activation and that forced expression of AKT completely reversed the inhibitory effect. HDM2 and p70S6K1 are two downstream targets of AKT that mediate growth factor-induced VEGF transcriptional activation and HIF-1␣ expression. The inhibition of PI3K by LY294002 inhibited p70S6K1 and HDM2 activity in the cells. Forced expression of p70S6K1 or HDM2 reversed LY294002-inhibited VEGF transcriptional activation and HIF-1␣ expression. This study identifies a potential novel mechanism responsible for increased VEGF expression in ovarian cancer cells. It also indicates the important role of VEGF and HIF-1 in ovarian tumorigenesis and angiogenesis, which is mediated by the PI3K/AKT/HDM2 and AKT/p70S6K1 pathways in ovarian cancer cells.

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“…Several study confirmed that VEGF expression level was negatively correlated with ovarian cancer prognosis (Hartenbach et al, 1997;Paley et al, 1997). Moreover, stage III clinical trials aslo showed apparent advantages of the anti-angiogenic agent (bevacizumab) in ovarian cancer (Burger et al, 2011;Perren et al, 2011;Aghajanian et al, 2012).…”

Section: Salvage Therapy Of Gemcitabine Plus Endostar Significantly Imentioning

confidence: 99%

Salvage Therapy of Gemcitabine Plus Endostar Significantly Improves Progression-free Survival (PFS) with Platinum-resistant Recurrent Epithelial Ovarian Cancer

Su¹,

Zhang²,

Pan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Vascular endothelial growth factor expression in early stage ovarian carcinoma

Cited by 332 publications

References 20 publications

Vasohibin-2 Expressed in Human Serous Ovarian Adenocarcinoma Accelerates Tumor Growth by Promoting Angiogenesis

Vasohibin-2 Expressed in Human Serous Ovarian Adenocarcinoma Accelerates Tumor Growth by Promoting Angiogenesis

Vascular Endothelial Growth Factor Transcriptional Activation Is Mediated by Hypoxia-inducible Factor 1α, HDM2, and p70S6K1 in Response to Phosphatidylinositol 3-Kinase/AKT Signaling

Salvage Therapy of Gemcitabine Plus Endostar Significantly Improves Progression-free Survival (PFS) with Platinum-resistant Recurrent Epithelial Ovarian Cancer

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