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

Abstract

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...

Role of αvβ5 integrins and vitronectin in Pseudomonas aeruginosa PAK interaction with A549 respiratory cells

“…Thus, the ECM protein-and integrin-mediated Pseudomonas adherence and uptake by A549 cells may be independent from the so-called CFTR innate immunity function [17]. The staining pattern obtained for avb5 integrins in A549 cells was evocative of a localization of these integrins in focal contacts, since they are quite similar to the staining obtained for other integrins in other cell lines [32,33]. The focal contact localization of these integrins strongly suggests that they actively participate in A549 cell behavior as part of functional heterodimers acting as signal transducers [34].…”

Reduced Growth, Increased Vascular Area, and Reduced Response to Cisplatin in CD13-Overexpressing Human Ovarian Cancer Xenografts

“…An explanation for the reduced invasion of CD13-overexpressing cells might be a decreased adhesion of the cells, which is required for proper invasion in the ECM (Ref. 26; also reviewed by Skubitz (27)]. Because we found only a moderate reduction in adhesion to Matrigel (30% reduction), it is questionable whether this explains the less invasive phenotype.…”

Study on the Expression and Clinical Significances of Lewis y Antigen and Integrin αv, β3 in Epithelial Ovarian Tumors

“…For instance, integrin αv, β3 is closely related to tumor invasion, metastasis and angiogenesis in ovarian cancer, malignant melanoma, breast cancer and prostate cancer [13]. Numerous studies have confirmed that integrin αv plays an important role in ovarian cancer progression and metastasis [14–17]. By activating integrin-linked kinase (IL-K), the integrin αv subunit promotes growth and proliferation of ovarian cancer cells, and mediates their adhesion and migration [18].…”