Implication of the αvβ3 integrin in the adhesion of the ovarian‐adenocarcinoma cell line IGROV1

Carreiras, Franck; Lehmann, Maxime; Sichel, François; Marvaldi, Jacques; Gauduchon, Pascal; Talaër, Jean-Yves Le

doi:10.1002/ijc.2910630413

Cited by 26 publications

(34 citation statements)

References 17 publications

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“…This expression is in agreement with its reported promotion of cell migration and proliferation (21,22). Subcellular localization aggregated in the cytoplasm of epithelial cells has also been reported in human pancreatic cancer cases (5).…”

Section: Discussionsupporting

confidence: 91%

Novel immunohistochemical marker, integrin αVβ3, for BOP-induced early lesions in hamster pancreatic ductal carcinogenesis

Kitahashi¹,

Yoshimoto²,

Imai³

2011

Oncology Letters

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Abstract. N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic ductal carcinomas and early ductal lesions in Syrian hamsters have been reported to show histopathological resemblance to those in humans. Specific protein expression profiles have been found in human carcinomas, but a detailed molecular approach regarding the dissection of BOP-induced pancreatic carcinogenesis has yet to be determined. The present immunohistochemical study of early and advanced hamster lesions focused on five proteins reported to be overexpressed in human patients, to clarify interspecies phenotype similarity. Integrin α V β 3 was found to be overexpressed in the epithelial cells of 13 of 14 atypical hyperplasias and 6 of 6 adenocarcinomas. This overexpression was more frequent than in the remaining four proteins. However, immunoreactivity for α-enolase in epithelial cells and for kallikrein 7 and galectin-1/3 in both epithelial and stromal cells was also evident at various frequencies. Thus, similarities of tumor-associated protein expression between human and hamster pancreatic ductal lesions were confirmed, and integrin α V β 3 was identified as a potentially useful immunohistochemical marker for early lesions in hamsters. IntroductionPancreatic cancer is among the 10 most frequently occurring type of cancer. In Japan, pancreatic cancer is ranked fifth as a cause of cancer-related mortality. The mortality rate associated with this type of cancer also ranks high in other developed countries (1,2). The detection of pancreatic cancer at early operable stages is difficult, combined with the lack of curative treatment approaches other than complete surgical removal; thus, 5-year relative survival rates are less than 6% (3,4). Therefore, it is crucial to develop new diagnostic and preventive methods to complement any improvements in therapeutic methods for the reduction of mortality and morbidity, and to explore specific proteins overexpressed in early lesions during pancreatic carcinogenesis.Specific protein expression profiles revealed by immunohistochemical and proteomic analyses are currently employed in the application of individualized therapy of advanced human pancreatic carcinomas (5-8). Consequently, a number of candidates of prognostic and/or predictive markers have been established (9,10). Examples expressed in early lesions show potential for the development of novel diagnostic and preventive strategies.Chemically induced and transgenic animal models for pancreatic ductal carcinogenesis have been the target of investigation of the impact of environmental factors and the role of specific gene alterations in multistage carcinogenesis (11)(12)(13)(14)(15). Among the models established thus far, the N-nitrosobis(2-oxopropyl)amine (BOP)-induced hamster model is the first and most widely utilized based on similarities to human diseases in the morphological characteristics of, not only advanced cancers, but also early ductal lesions, as well as pivotal genetic alterations, including K-ras and p16 (13,(16)(17)(18). In particular...

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Section: Discussionsupporting

confidence: 91%

Novel immunohistochemical marker, integrin αVβ3, for BOP-induced early lesions in hamster pancreatic ductal carcinogenesis

Kitahashi¹,

Yoshimoto²,

Imai³

2011

Oncology Letters

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“…The importance of a v integrins in adhesion and migration has been reported previously in the case of different cancers (Friedlander et al, 1996;Van Leeuwen et al, 1996;Wong et al, 1998;Zheng et al, 2000) including ovarian cancer (Carreiras et al, 1995(Carreiras et al, , 1999a. The role of a v integrins, in cooperation with growth factors, in mediating cell growth in the context of angiogenesis has been well described (Eliceiri and Cheresh, 2001).…”

Section: Introductionmentioning

confidence: 65%

“…In this report, we investigate the role of a v integrins in the regulation of cell proliferation. We chose as models two human ovarian cancer cell lines: IGROV1, in which a v b 3 is the sole member of the a v integrins family and SKOV-3, which express both a v b 3 and a v b 5 (Cannistra et al, 1995;Gardner et al, 1995;Carreiras et al, 1995Carreiras et al, , 1999a. We have analysed the effects of blocking the a v integrins on IGROV1 and SKOV-3 cell proliferation and determined which intracellular signaling proteins linked to integrins were involved in this process.…”

Section: Introductionmentioning

confidence: 99%

αv integrins regulate cell proliferation through integrin-linked kinase (ILK) in ovarian cancer cells

et al. 2003

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Integrins regulate both adhesion and signaling processes involved in proliferation and survival. a v b 3 and a v b 5 integrins have been shown to mediate cell adhesion and migration. Here we used human ovarian cancer cell lines (IGROV1, SKOV-3) that express a v b 3 and a v b 5 to study their role in cell proliferation and the signaling pathways involved. We found that a v integrins regulate cell proliferation through activation of integrin-linked kinase (ILK). An anti-a v -blocking antibody specifically inhibits the growth of IGROV1 and SKOV-3. The inhibition of cell proliferation involves a v b 3 in IGROV1 cells, and both a v b 3 and a v b 5 in SKOV-3 cells. The reduced growth rate induced by a v integrin blockade is linked in both cell lines to G1/S cell cycle arrest. a v integrin blockade by neutralizing antibody as well as cyclic-RGD peptide caused an inhibition of ILK activity and phosphorylation of PKB/Akt on serine-473 but not on threonine-308, and was accompanied by an increase in p27Kip1 expression. Overexpression of wild-type ILK rescued the phosphorylation of PKB/Akt on serine-473 in cells treated with anti-a v antibody. Inhibition of ILK by a pharmacological inhibitor results in inhibition of cell proliferation, PKB/ Akt phosphorylation and increase of p27Kip1 . These results demonstrate that a v integrins regulate ovarian cancer cell proliferation through ILK.

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“…This result confirms integrin involvement but also suggest the contribution of RGD-independent integrins or other adhesion molecules such as proteoglycans. 24 The adhesion assays using antiintegrin antibodies revealed the implication of ␣v␤3, the only ␣v integrin expressed by IGROV1 cells 25 and ␤1 integrins. ␣v␤3 alone can support in part the adhesion as oppose to ␣5␤1.…”

Section: Discussionmentioning

confidence: 99%

Involvement of αvβ 3 integrin and disruption of endothelial fibronectin network during the adhesion of the human ovarian adenocarcinoma cell line IGROV1 on the human umbilical vein cell extracellular matrix

Carreiras

Thiébot

Leroy-Dudal³

et al. 2002

Intl Journal of Cancer

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Key words: extracellular matrix; integrin; ovarian carcinoma; HUVECsNeoangiogenesis is the complex process by which new blood vessels are generated from preexisting vessels. The growth of new blood vessels plays a critical role in a variety of normal physiological events but also in pathological processes. 1 In the case of tumoral angiogenesis, the process is under cell tumor influence and conversely the expansion of solid tumors is critically dependent on vascular networks that provide nutrients for growing tumors and allow metastasis in distant organs. 2 The interaction of tumors with the vasculature is an important step in the metastatic cascade. The identification of molecules that play a functional role in tumor neovascularization, especially in the interactions of tumor cells with endothelial extracellular matrix underlining the vasculature, has been investigated for several years and the potential role of cell adhesion molecules and their ligands are of interest. 2 The integrins represent the main extracellular matrix (ECM) receptors that are composed of ␣ and ␤ chains that combine to give 23 heterodimers with distinct cellular and adhesive specificities. 3,4 These transmembrane glycoproteins are expressed by endothelial cells as well as by a variety of tumor cells. It was shown that integrin ␣v␤3 can provide specific cell survival signals that facilitate vascular cell proliferation during angiogenesis. 5 This integrin appeared also to be strongly involved in several tumor cell growth such as melanoma and breast cancer. 6,7 ␣v␤3 is a receptor for a wide variety of ECM proteins; among them, fibronectin (Fn) has been involved in tumor development and angiogenesis. 8 Indeed, endothelial cell motility is promoted by binding ECM proteins such as Fn to integrins and interfering with this step may inhibit the process of angiogenesis. 9 Ovarian carcinoma is one of the most common fatal gynecological malignancies and for the majority of patients, these tumors are diagnosed at advanced stages. 10 The ovarian tumors arise mainly from the malignant transformation of ovarian surface epithelium (OSE) cells. These cells spread out and disseminate into the peritoneal cavity to give intra-abdominal grafts whereas metastases in distant organs occurred late. There are only few reports regarding angiogenesis in patients with advanced ovarian carcinoma. Quantification and evaluation of vascular density in ovarian cancer revealed that tumor angiogenesis is a prognostic factor. 11,12 Little is known, however, about the cellular processes that lead to ovarian carcinoma neovascularization. Because several studies demonstrated the primordial role of integrins in ovarian cancer behavior, in particular of ␣v␤3 integrin and their ligands, 13-15 we focused our interest on the role of this integrin in the interactions between ovarian tumor and its vasculature.In our study, we therefore used in vitro models, IGROV1 human ovarian adenocarcinoma cell line and human umbilical vein endothelial cells (HUVECs) to analyze the adhesion properti...

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Implication of the αvβ3 integrin in the adhesion of the ovarian‐adenocarcinoma cell line IGROV1

Cited by 26 publications

References 17 publications

Novel immunohistochemical marker, integrin αVβ3, for BOP-induced early lesions in hamster pancreatic ductal carcinogenesis

Novel immunohistochemical marker, integrin αVβ3, for BOP-induced early lesions in hamster pancreatic ductal carcinogenesis

αv integrins regulate cell proliferation through integrin-linked kinase (ILK) in ovarian cancer cells

Involvement of αvβ 3 integrin and disruption of endothelial fibronectin network during the adhesion of the human ovarian adenocarcinoma cell line IGROV1 on the human umbilical vein cell extracellular matrix

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