αV- and β1-integrin subunits are commonly expressed in malignant effusions from ovarian carcinoma patients

Davidson, Ben; Goldberg, Iris; Reich, Reuven; Tell, Liora; Dong, Hiep Phuc; Tropé, Claes G.; Risberg, Bjørn; Kopolovic, Juri

doi:10.1016/s0090-8258(03)00321-4

Cited by 74 publications

(56 citation statements)

References 33 publications

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“…1b). The a 2 b 1 integrin is widely expressed on ovarian cancers, 13,15 and a similar pattern of the a 2 b 1 integrin has been observed on ovarian cancer cell lines as on primary ovarian tissue samples. 23 This demonstrates that the integrin expression on ovarian cancer cell lines is not only a feature of cultured cells.…”

Section: Enterovirus-mediated Oncolysis Of Ovarian Cancer Cellssupporting

confidence: 58%

“…One enteroviral cellular receptor molecule widely expressed on ovarian cancer cells at high levels on the cell surface is integrin a 2 b 1 . 13,14 This integrin is strongly expressed on both primary epithelial ovarian tumors and metastatic tumor cells in ascites samples, while only weak staining is present on normal surface epithelium. 13,15 EV1 is a human enterovirus that attaches to target cells via interactions with surfaceexpressed integrin a 2 b 1 16,17 and is postulated to enter cells via a caveolae-dependent mechanism.…”

mentioning

confidence: 99%

“…13,14 This integrin is strongly expressed on both primary epithelial ovarian tumors and metastatic tumor cells in ascites samples, while only weak staining is present on normal surface epithelium. 13,15 EV1 is a human enterovirus that attaches to target cells via interactions with surfaceexpressed integrin a 2 b 1 16,17 and is postulated to enter cells via a caveolae-dependent mechanism. 18 Crystallographic studies indicate that EV1 binds to the I domain of integrin a 2 b 1 , which consists of a 200-amino acid region similar to other domains in a 2 leukocyte integrins, von Willebrand's factor, cartilage matrix protein and complement proteins.…”

mentioning

confidence: 99%

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Oncolysis of human ovarian cancers by echovirus type 1

Shafren

Sylvester

Johansson

et al. 2005

Intl Journal of Cancer

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A small number of enteroviruses possess the capacity to induce rapid and marked lytic infections in cells of various human malignancies. During screening of representative human enteroviruses for their oncolytic capacity, we observed that echovirus type 1 (EV1) displayed a high level of tropism for human ovarian cancer cells. EV1 is an enterovirus which largely causes asymptomatic infections in humans and whose tissue tropism is primarily regulated via interactions with the I domain of the a subunit of cell surface-expressed integrin a 2 b 1 . We evaluated the capacity of wildtype EV1 to act as an oncolytic agent of ovarian cancers propagated as cell monolayers, multicellular spheroids or xenografts in SCID mice. EV1 infection of in vitro propagated ovarian cell lines expressing high levels of integrin a 2 b 1 was assessed for specific viral attachment, antibody blockade, induction of cytopathic effect and production of progeny virions. EV1 lytically infected all 8 human ovarian cancer cell lines tested (2008, DOV13, JAM, OVCA-429, OVCAR-3, OVHS-1, OAW-42 and IGROV-1) but not the immortalized normal ovarian surface epithelial cell line (HOSE) or human PBMCs. EV1 challenge was equally effective in the oncolysis of human ovarian cancer cells whether in monolayer or spheroidal environments. The therapeutic efficacy of EV1 was demonstrated by rapid reduction of tumor burden by a single viral intratumoral injection in SCID mice bearing multiple preformed s.c. xenografts. Using an in vivo i.p. human ovarian cancer xenograft model, administration of EV1 was further shown to significantly inhibit the formation and burden of ascites tumors. These findings demonstrate an important proof of principle for employing wild-type EV1 as a potential oncolytic agent in the control of human ovarian cancers. ' 2005 Wiley-Liss, Inc.

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Section: Enterovirus-mediated Oncolysis Of Ovarian Cancer Cellssupporting

confidence: 58%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Oncolysis of human ovarian cancers by echovirus type 1

Shafren

Sylvester

Johansson

et al. 2005

Intl Journal of Cancer

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“…Davidson et al (16) reported that the αv-and β1-integrin subunits are frequently expressed in ovarian cancer cells in effusions, and that the αv-integrin subunit is a powerful diagnostic marker for ovarian cancer cells. They concluded that the high expression of integrin subunits, which play roles in binding mesothelium, invasion, and angiogenesis in carcinoma cells in both peritoneal and pleural effusions, suggests that cells at both sites have metastatic potential.…”

Section: Discussionmentioning

confidence: 99%

The potent peptide antagonist to angiogenesis, C16Y, and cisplatin act synergistically in the down-regulation of the Bcl-2/Bax ratio and the induction of apoptosis in human ovarian cancer cells

Shinagawa

Yoshida

Kurokawa³

et al. 2011

Int J Oncol

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Abstract. Cisplatin is one of the most potent antitumor agents for ovarian cancer, but has also been implicated in normal tissue cytotoxicity. We examined the effect of cisplatin alone and in combination with C16Y, a newly-identified anti-angiogenic peptide from the NH 2 -terminal domains of the γ-chain of laminin-1, on the modulation of Bcl-2/Bax expression and induction of apoptosis in ovarian cancer cells (OVACAR3). C16Y did not elicit cell death of human umbilical vein endothelial cells (HUVECs). Cisplatin exerted a lethal effect with an EC 50 of 10 µM in OVACAR3s. In the presence of 25 or 50 µg/ml of C16Y (a range which has no effect against HUVECs), the EC 50 for cisplatin in OVACAR3s decreased to 3.5 and 2.0 µM, respectively. Using fluorescence-activated cell sorting (FACS) analysis of DNA stained OVACAR3s and terminal deoxynucleotide tranferase-mediated dUTP nick end-labeling (TUNEL), we found that even at concentrations of 1 and 3 µM cisplatin, C16Y at 10 and 25 µg/ml increased the incidence of apoptosis in OVACAR3s by 3-5-fold. Each drug had some measurable effect on Bax protein expression. Furthermore, Bcl-2 protein expression levels were markedly reduced by C16Y alone and cisplatin alone in a dose-dependent manner. The combination of C16Y and cisplatin resulted in a further dramatic reduction in Bcl-2, underscoring the pronounced synergy produced by cisplatin and C16Y together. On the other hand, C16Y did not activate any other signal transduction pathways that usually culminate in the activation of apoptosis, such as the p53, p21 waf1 , p73, ERK1/2 or PI3-AKT pathways. These observations suggest that the suppression of the Bcl-2/Bax ratio may play an important role in mediating the synergistic effect of cisplatin and C16Y on the induction of apoptosis in OVACAR3 cells.

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“…65 Increased β1 integrin expression has also been found in ovarian carcinoma cells isolated from pleural effusions as compared with primary ovarian tumor cells. 66 The β1 integrin-fibronectin interaction has also been suggested to be important in determining metastatic potential, as a study looking at breast cancer cells with varying degrees of metastatic ability showed a fibronectindependent, β1 integrin-mediated control over the ability of metastatic cells to sense the rigidity of the microenvironment; 67 an effect that could contribute to the increased metastatic ability of cells expressing higher levels of β1 integrin.…”

Section: B1 Integrin In Metastasismentioning

confidence: 99%