Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epithelial cancer of the ovary spreads by implantation of tumor cells onto the mesothelial lining of the peritoneal cavity. We have developed an in vitro binding assay using confluent monolayers of normal peritoneal mesothelial cells in order to assess the role of known adhesion proteins in this process. Cells from normal ovarian surface epithelium and the ovarian cancer cell lines CAOV-3 and SKOV-3 exhibited significant adhesion to mesothelium in vitro (range 33-56% specific binding). Although these cells expressed several adhesion molecules, including CD44 and integrins such as alpha 4 beta 1, alpha 5 beta 1, and alpha v beta 3, only anti-CD44 antibody was capable of inhibiting mesothelial binding (range 42-44% inhibition). Adhesion molecule expression was also determined for fresh ovarian specimens, with CD44 being expressed in 2 of 2 cases of normal ovarian epithelium, 15 of 16 (94%) cases of tissue-derived tumor (from primary sites or peritoneal implants), and only 2 of 8 (25%) cases of free-floating tumor cells from ascites. Three of three CD44-positive cases derived from peritoneal implants exhibited significant mesothelial binding which was partly blocked by anti-CD44 antibody, whereas 2 of 2 CD44-negative cases derived from ascites showed minimal binding. CD44-mediated binding of ovarian cancer cells was determined to be due to recognition of mesothelium-associated hyaluronate, suggesting that the CD44H isoform was involved in this process. Immunoprecipitation of the CD44 species expressed by ovarian cancer cells revealed 2 major bands at 85-90 and 180 kDa, consistent with the known molecular masses of CD44H. These results suggest that CD44H may be an important mediator of ovarian cancer cell implantation and that decreased CD44H expression may be associated with release of cells into the peritoneal space during ascites formation. It is possible that strategies to interfere with CD44H function may result in decreased intraabdominal spread of this highly lethal neoplasm.
 ...
PMID:Binding of ovarian cancer cells to peritoneal mesothelium in vitro is partly mediated by CD44H. 833 95

The effects of pelvic and periaortic peritoneal closure or (non-closure) on morbidity and adhesion formation were prospectively compared in 102 patients with ovarian cancer who had undergone a pelvic and periaortic lymphadenectomy. Hysterectomy with bilateral salpingoophorectomy, bilateral pelvic and periaortic lymphadenectomy, omentectomy, appendectomy and lysis of pelvic adhesions for the standardization of initial adhesion scores was performed on all patients. The pelvic and periaortic peritoneum were re-approximated in group I (n = 50) patients, and left open in group II (n = 52) patients. The groups were similar for mean age, previous surgery, tumour histology and disease stage. Morbidity characteristics such as blood loss, transfusion rate, post-operative infectious and non-infectious complications, and total hospital stay were also similar. After six courses of PAC (cisplatin 50 mg/m(2), Adriamycin 50 mg/m(2), cyclophosphamide 500 Mg/M(2)) chemotherapy, all patients underwent a second-look laparotomy. Persistent cancer was detected in 49 of 102 (48.03%) patients. Adhesion scores were detected at the time of second-look laparotomy. Adhesion scores for group I (8.9 +/- 2.9) were significantly higher than the group II (peritoneum non-closure) (5.8 +/- 2.3) (P<0.01). Closing the pelvic and periaortic peritoneum did not effect morbidity, but leaving the pelvic and periaortic peritoneum open significantly decreased the adhesion formation.
 ...
PMID:Pelvic and periaortic pertioneal closure or non-closure at lymphadenectomy in ovarian cancer: effects on morbidity and adhesion formation. 865 13

Our previous studies have suggested that the interaction between hyaluronic acid (HA) on peritoneal mesothelial cells and the membrane adhesion molecule, CD44, on ovarian tumour cells could be important in ovarian cancer metastasis. In order to study this further, adhesion of six ovarian tumour lines to HA coated on to a plastic surface was investigated. Four lines bound to the HA coat and two lines did not. The adhesive lines were those that expressed high amounts of CD44, but the degree of adhesion was not closely correlated with CD44 expression. The results suggested that different tumour lines had different affinities for HA. Treatment of the HA coat with hyaluronidase substantially reduced adhesion. Adhesion was also partially reduced if the tumour cells were preincubated with either soluble HA, or anti-CD44 antibodies directed against the HA binding region. An antibody against a non-HA binding region only slightly blocked adhesion at high antibody concentrations. Only the CD44H isoform was detected by immunoprecipitation on the tumour cells. These results suggest that ovarian tumour cells can attach to immobilised HA via CD44H on the cell membrane.
 ...
PMID:Human ovarian tumour cells can bind hyaluronic acid via membrane CD44: a possible step in peritoneal metastasis. 887 6

The adhesion of tumour cells to the hyaluronan (HA) pericellular coat of mesothelial cells is an important step in the peritoneal spread of ovarian cancer. Previously, we have shown that the cell surface molecule CD44 is involved in this process. Paradoxically, the degree of adhesion does not appear to be related to the amount of CD44 expressed. In order to explain this observation we have examined the in vitro adhesion to HA of four high CD44-expressing ovarian cancer lines in relation to their CD44 spliced variant content and the CD44 glycosylation. Adhesion was measured in multiwell plates coated with different concentrations of HA in order to determine both the avidity and the maximum adhesion. Two lines had high adhesion and two lines had low adhesion. The avidity for HA was different for each line, but in all cases this could be totally blocked by treatment with an anti-CD44 antibody. The standard form of CD44 was the major species detected by RT/PCR in all lines and spliced variants were present in low amounts. Neuraminidase treatment increased the adhesion of the 'low-adhesion' lines at all HA coating concentrations; but only substantially increased the adhesion of the 'high-adhesion' lines at the lower HA coating concentrations. Tunicamycin treatment decreased the adhesion of the 'high-adhesion lines' at all HA coating concentrations and only substantially decreased the adhesion of one of the 'low-adhesion' lines when the plates were coated with a low concentration of HA. The adhesion of the remaining 'low-adhesion' line was slightly increased after tunicamycin treatment. It is concluded that glycosylation and not spliced variant content of CD44 affects the adhesive properties of ovarian tumour cells. This conclusion may have important consequences for developing new therapies in ovarian cancer.
 ...
PMID:Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan. 1084 57

Like the majority of tumor cells, ovarian cancer cell growth is critically dependent on their neovascularization. Adhesion molecules and cellular events that lead to ovarian tumor cell interactions with endothelial extracellular matrix surrounding the vasculature are poorly identified. To understand the role of alphavbeta3 integrin and its ligand fibronectin in this process, we used in vitro coculture models with IGROV1 human ovarian adenocarcinoma cell line and human umbilical vein endothelial cells (HUVEC). Adhesion assays revealed a strong ability of IGROV1 cells to adhere to HUVEC-ECM. alphavbeta3 is mainly implicated and seems to cooperate with alpha5beta1 integrin in this event. Immunofluorescence staining revealed the presence of alphavbeta3 and alpha5beta1 in IGROV1 cells adhering on HUVEC-ECM at regions of cell sub-stratum contacts. Furthermore, our data showed the absence of fibronectin staining in IGROV1 cells and the disruption of the HUVEC-ECM fibrillar fibronectin network under IGROV1 cell influence. In situ experiments in ovarian neoplastic tissue corroborated the absence of fibronectin in the tumor and its strong detection in vasculature. These findings suggest the active participation of alphavbeta3 and alpha5beta1 integrins and the reorganization of endothelial fibronectin during the adhesion of IGROV1 cells to HUVEC-ECM whereas IGROV1 cells seem to be unable to synthesize fibronectin. Thus, fibronectin integrin receptors expressed by ovarian tumor cells and endothelial fibronectin may be of importance in ovarian carcinoma neovascularization and during tumor-vasculature interactions.
 ...
PMID:Involvement of alphavbeta 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. 1211 80

During tumor metastasis, a fine-tuned balance between the formation and loosening of adhesive cell contacts has to occur, a process based on the regulated expression of integrins. Human ovarian OV-MZ-6 cancer cells express the integrin alpha(v)beta3, which associates with vitronectin (VN) and correlates with ovarian cancer progression. Adhesion and spreading of OV-MZ-6 cells on VN was accompanied by the formation of focal adhesion contacts and the recruitment of activated tyrosine-phosphorylated focal adhesion kinase. Cultivation of OV-MZ-6 cells on VN resulted in a significantly induced cell proliferation. This VN effect could be mimicked by cultivating cells on the immobilized alpha(v)beta3 directed peptide cyclo-Arg-Gly-Asp-D-Phe-Val (cRGDfV). VN-dependent OV-MZ-6 cell adhesion and proliferation was significantly enhanced by overexpression of alpha(v)beta3 and was accompanied by rapid and transient tyrosine-phosphorylation of p44(erk-1)/p42(erk-2) mitogen-activated protein kinase. Moreover, overexpression of alpha(v)beta3 and OV-MZ-6 cell attachment to VN increased cell motility up to 5-fold accompanied by prominent changes in cytoskeletal organization and cell morphology. Upon alpha(v)beta3/VN interaction, by cDNA expression microarray analysis we identified altered mRNA levels of c-myc, epidermal growth factor receptor (EGF-R), transcription factor Fra-1, prothymosin-alpha (PTMA), integrin-linked kinase (ILK), and the cell adhesion molecule SQM-1, candidates which are possibly involved in changes of the adhesive, migratory, and proliferative phenotype of human ovarian cancer cells.
 ...
PMID:Ovarian cancer cell proliferation and motility is induced by engagement of integrin alpha(v)beta3/Vitronectin interaction. 1295 24

Integrins play an important role in cellular matrix interactions requisite for cancer cell adhesion, growth, migration and invasion. In this study, we have investigated the expression of integrin subunits alpha3, alpha6, alphav and beta1 in normal ovaries, benign ovarian tumors and ovarian carcinomas of different pathological grades. The expression of these integrins in ovarian cancer cell lines was also investigated, and their role in sustaining proliferation, adhesion, migration and invasion in cohort with the activation of signaling pathways in response to extracellular matrices (ECM) was evaluated. We demonstrate a differential expression pattern of alpha3, alpha6, alphav and beta1 integrin subunits in ovarian carcinomas compared to normal ovaries and benign ovarian tumors. Ovarian cancer cell lines (Hey, Ovcar3 and Peo.36) demonstrated significantly high expression of alpha3, alpha6, alphav and beta1 integrin subunits. A significant increase in proliferation and adhesion (P<0.05) in response to collagen 1 (Coll) and laminin (LM), ligands for integrin receptor alpha3beta1 and alpha6beta1 was observed in ovarian cancer cell lines. On the other hand, fibronectin (FN), a receptor for alphavbeta1 integrin, increased proliferation in all ovarian cancer cell lines studied but only enhanced adhesion in Hey cell line (P<0.05). Neutralizing antibodies against alpha3, alpha6, alphav and beta1 integrin subunits inhibited ECM-induced proliferation, but increased adhesion to ECM was inhibited by beta1 integrin subunit antibody. No suppression of Coll, LM and FN-induced (Hey cells only) adhesion was observed in the presence of alpha3 or alphav subunit antibodies but LM-induced adhesion was inhibited by blocking alpha6 subunit functions. LM, FN and Coll enhanced chemotactic migration in Hey cells, but direct invasion across ECM was observed only in the presence of LM and Coll. Blocking antibodies against alpha3, alpha6 and beta1 integrin subunits inhibited both chemotactic migration and invasion of Hey cells in response to respective ECM. Adhesion of ovarian cancer cells to FN, Coll and LM activated Ras, Erk and Akt pathways. Neutralizing alphav and beta1 functions did not inhibit FN-induced activation of Ras and Erk pathways but inhibited the Akt pathway. On the other hand, antibodies against alpha6 and beta1 subunits, but not alpha3 subunit, inhibited LM-induced activation of Ras but did not inhibit the downstream Akt pathway. Neutralizing beta1 subunit function however, inhibited LM-induced Erk activation. Coll-induced activation of Ras, Erk and Akt pathways was inhibited by alpha3 and beta1 integrin subunit antibodies. These results indicate that alpha3beta1, alphavbeta1 and alpha6beta1 integrin mediate proliferation, adhesion, migration and invasion of ovarian cancer cells in response to ECM and targeting these integrins to modulate integrin-ECM interactions in tumor cells may be a promising tool to reduce the dissemination of ovarian carcinoma in vivo.
 ...
PMID:Role of integrin receptors for fibronectin, collagen and laminin in the regulation of ovarian carcinoma functions in response to a matrix microenvironment. 1628 82

Epithelial ovarian cancer cells metastasize by implanting onto the peritoneal mesothelial surface of the abdominal cavity. Adhesive molecules that lead to this implantation remain unclear. The aim of our study was to focus on the role of vitronectin (Vn) and its receptors, alpha(v) integrins and urokinase plasminogen activator receptor (uPAR), in the interactions of ovarian adenocarcinoma cells (IGROV1 and SKOV3 cell lines) with mesothelial cells (MeT-5A cell line and primary cultures). For all cell lines, immunofluorescence staining disclosed the presence of Vn over the whole cell surface and in thin continuous deposits underlining the cell periphery. Recruitment of Vn receptors to cell-cell contact sites was also revealed. We developed two distinct methods for the evaluation of in vitro cell-cell adhesion using cocultures of the tumor and mesothelial cells. Both adhesion assays revealed a strong ability of ovarian cancer cells to adhere preferentially to mesothelial intercellular junctions. Adhesion of ovarian carcinoma cells to mesothelial cells was significantly inhibited using anti-Vn-, -alpha(v)-integrin- and -uPAR-blocking antibodies or cyclic peptide cRGDfV. These results evidence the ability of ovarian carcinoma cells to bind to peritoneal mesothelium in vitro and strongly suggest that Vn and its receptors contribute to this crucial event.
 ...
PMID:Vitronectin and its receptors partly mediate adhesion of ovarian cancer cells to peritoneal mesothelium in vitro. 1878 Oct 95

Adhesion of ovarian cancer cells to the peritoneal mesothelium is a key step in the malignant progression of the disease. In an in vitro study, we showed that the adherence of ovarian cancer cells (of the OVCAR-3, SKOV-3, and A2780 cell lines) to senescent human omentum-derived peritoneal mesothelial cells (HOMCs) was greater than to early passage cells. The process was mediated primarily by the increased interaction of the alpha5beta1 integrin on cancer cells with HOMC-associated fibronectin (FN). In comparison with early passage HOMCs, senescent cells exhibited increased FN mRNA expression levels and produced significantly more FN. To assess the effect of senescence-associated oxidative stress on FN release, HOMCs were rendered senescent by exposure to an oxidant, tert-butyl hydroperoxide. Treatment with tert-butyl hydroperoxide resulted in a significant increase in HOMC FN mRNA and protein expression levels. The effect of oxidative stress on FN synthesis was found to be mediated by transforming growth factor-beta1, whose signaling pathway was controlled at upstream and downstream levels by p38 MAPK. The activity of p38 MAPK increased markedly in senescent HOMCs. Treatment of HOMCs with antioxidants significantly attenuated senescence-associated increases in p38 MAPK activity, production of both transforming growth factor-beta1 and FN, and ovarian cancer cell adhesion. These data indicate that oxidative stress that accompanies senescence may increase FN production by HOMCs and thus facilitate binding and dissemination of ovarian cancer cells.
 ...
PMID:Senescent peritoneal mesothelial cells promote ovarian cancer cell adhesion: the role of oxidative stress-induced fibronectin. 1924 46

This study was aimed to explore the role of stromal-derived factor 1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis in mediating the metastasis of ovarian cancer cells through activation of extracellular signal-regulated kinase-1/2 (ERK-1/2) signaling pathway. A highly metastatic ovarian cancer cell line, SKOV3, was used in the study. Intracellular calcium mobilization was detected by using laser scanning confocal fluorescence microscopy. Western blotting was used to detect the phosphorylation of ERK1/2 in SDF-1alpha-treated SKOV3 cells. Adhesion capability and matrix metalloproteinase (MMP) activity of ovarian cancer cells after exposure to SDF-1alpha were measured by adhesion assay and gelatin zymography. The results showed that SDF-1alpha induced rapid intracellular calcium mobilization in SKOV3 cells, as well as the phosphorylation of ERK-1/2. The adhesion of ovarian cancer cells to fibronectin and collagen IV was increased after SDF-1alpha treatment. An inhibitor of ERK-1/2 signaling, PD98059, could antagonize such effects of SDF-1alpha. SDF-1alpha could also increase the secretion of active MMP-2 and MMP-9. It was concluded that the SDF-1/CXCR4 axis played a critical role in the metastasis of human ovarian cancer by increasing the adhesion capability of cancer cells and the activity of MMP-2 and MMP-9 via ERK1/2 signaling pathway.
 ...
PMID:The role of SDF-1/CXCR4 axis in ovarian cancer metastasis. 1951 23


1 2 Next >>