Modulation of Angiogenic Phenotype Alters Tumorigenicity in Rat Ovarian Epithelial Cells

Schumacher, Jennifer J.; Dings, Ruud P.M.; Cosin, Jonathan A.; Subramanian, Indira V.; Auersperg, Nelly; Ramakrishnan, Sundaram

doi:10.1158/0008-5472.can-06-3608

Cited by 33 publications

(19 citation statements)

References 37 publications

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“…Furthermore CD31 staining of the tumor tissues of AuNP-treated mice also demonstrated a reduction in the number of tumor blood vessels compared with NT mice, consistent with the inhibitory effect of AuNPs toward HB-GF (Fig. 3 F and G) (45)(46)(47). Moreover, AuNP-mediated reversal of EMT and abrogation of MAPK activation leading to inhibition of tumor growth and metastasis was further confirmed by analysis of tumor tissues by Western blot analysis (Fig.…”

Section: Aunp Treatment Inhibits Tumor Growth and Metastasis In Vivo Bysupporting

confidence: 73%

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Arvizo¹,

Saha²,

Wang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

213

215

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Although biomedical applications of nanotechnology, which typically involve functionalized nanoparticles, have taken significant strides, biological characterization of unmodified nanoparticles remains underinvestigated. Herein we demonstrate that unmodified gold nanoparticles (AuNPs) inhibit the proliferation of cancer cells in a size-and concentration-dependent manner by abrogating MAPK-signaling. In addition, these AuNPs reverse epithelial-mesenchymal transition (EMT) in cancer cells by reducing secretion of a number of proteins involved in EMT, up-regulating E-Cadherin, and down-regulating Snail, N-Cadherin, and Vimentin. Inhibition of MAPK signaling and reversal of EMT upon AuNP treatment inhibits tumor growth and metastasis in two separate orthotopic models of ovarian cancer. Western blot analyses of tumor tissues reveal up-regulation of E-Cadherin and down-regulation of Snail and phospho-MAPK, confirming the reversal of EMT and inhibition of MAPK signaling upon AuNP treatment. The ability of a single selftherapeutic nanoparticle to abrogate signaling cascades of multiple growth factors is distinctive and purports possible medical applications as potential antitumor and antimetastatic agent.drug delivery | heparin-binding growth factors

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Section: Aunp Treatment Inhibits Tumor Growth and Metastasis In Vivo Bysupporting

confidence: 73%

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Arvizo¹,

Saha²,

Wang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

213

215

View full text Add to dashboard Cite

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“…These findings point to an additional important role for VEGF in ovarian cancer invasion. VEGF plays a critical role in ovarian cancer progression by enhancing vascular permeability, promoting new vessel growth and inducing ascites formation, and hence, tumor cell dissemination (22). In addition, this study shows that by promoting host MMP9 expression, tumor VEGF enhances the tumor cell's invasive potential.…”

Section: Discussionmentioning

confidence: 63%

Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Belotti

Calcagno

Garofalo

et al. 2008

Molecular Cancer Research

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Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP) regulate each other, contributing to tumor progression. We have previously reported that MMP9 induces the release of tumor VEGF, promoting ascites formation in human ovarian carcinoma xenografts. The aim of this study was to investigate whether tumor-derived VEGF regulated the expression of gelatinase by the stroma, influencing the invasive properties of ovarian tumors. Tumor variants derived from 1A9 human ovarian carcinoma, stably expressing VEGF 121 in the sense (1A9-VS-1) and antisense orientations (1A9-VAS-3), were used. In vivo, zymographic analysis of tumors from 1A9-VS-1 implanted in the peritoneal cavity of nude mice showed higher levels of gelatinases, particularly murine MMP9, indicating that VEGF stimulates host expression of the matrix-degrading enzyme. Murine MMP9 expression was also high in the ovaries of mice bearing 1A9-VS-1 tumors. The effect on host MMP9 activity was organ-specific. The levels of host pro-MMP9 in ovaries correlated with the plasma levels of tumor VEGF and with the selective invasion of the ovaries. Induction of host MMP9 expression in tumors and ovaries was independent of the site of tumor growth as it was seen in mice carrying both intraperitoneal and subcutaneous tumors. The anti-VEGF antibody bevacizumab (Avastin) inhibited MMP9 expression and tumor invasion in the ovaries of mice bearing 1A9-VS-1 tumors. These findings point to a complex cross-talk between VEGF and MMPs in the progression of ovarian tumor and suggest the possibility of using VEGF inhibitors to affect MMP-dependent tumor invasion.

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“…Opipari and colleagues (2004) has shown that resveratrol induces death in ovarian cancer cells by autophagocytosis, a mechanism distinct from apoptosis, suggesting that it may provide leverage to treat ovarian cancer that is chemoresistant on the basis of ineffective apoptosis. Further, alterations in the angiogenic characteristics of ovarian surface epithelium may play an important role in the etiology of ovarian cancer (Schumacher et al, 2007). Human ovarian cancer progression and angiogenesis were reduced by resveratrol through suppression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) as observed (Cao et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Exerts Differential Effects in Vitro and in Vivo against Ovarian Cancer Cells

Stakleff¹,

Sloan²,

Blanco³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Epithelial ovarian cancer represents the most lethal gynecological cancer, and the high mortality rate makes this malignancy a major health concern. Poor prognosis results from an inability to detect ovarian cancers at an early, curable stage, as well as from the lack of an effective therapy. Thus, effective and novel strategies for prevention and treatment with non-toxic agents merit serious consideration. Resveratrol, obtained from grapes, berries, peanuts and red wine, has been shown to have a potent growth-inhibitory effect against various human cancer cells as well as in in vivo preclinical cancer models. The objective here was to evaluate potential antitumor effects of resveratrol in both in vitro and in vivo NuTu-19 ovarian cancer models. In vitro an invasion assay was performed. After 48 h, the numbers of viable cells that invaded the extracellular matrix layer were reduced by 94% with resveratrol in comparison to control. For the in vivo anti-tumor assessment, 10 rats were injected with NuTu-19 cells into the ovarian bursa. Thereafter, half were provided with a diet mixed with a dose of 100 mg resveratrol/kg body weight/day for 28 days. Following sacrifice, anticancer effects were assessed by histological evaluation of ovarian as well as surrounding tissues, and immunohistochemical detection of cell proliferation and apoptosis, but there were no observable differences between the control and resveratrol-treated groups for any of the biological endpoints. While resveratrol is effective in suppressing the in vitro cellular invasion of NuTu-19 ovarian cancer cells, these effects do not appear to impact on in vivo NuTu-19 ovarian cancers in rats.

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Modulation of Angiogenic Phenotype Alters Tumorigenicity in Rat Ovarian Epithelial Cells

Cited by 33 publications

References 37 publications

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion

Resveratrol Exerts Differential Effects in Vitro and in Vivo against Ovarian Cancer Cells

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