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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

VLA-6 (alpha6beta1) integrin represents the major receptor for interaction with laminin substrate. It has been proposed that VLA-6 mediates tumor cell adhesion to the endothelium during extravasation. We have further explored this possibility using mouse melanoma B16F1 cells, which express VLA-6 as the principal laminin receptor, and two VLA-6 monoclonal antibodies (mAbs), MA6 and GoH3. Adhesion is a prerequisite of cell movement on matrix proteins. Thus, GoH3, which inhibited VLA-6-mediated adhesion, blocked cell movement on laminin. The recently prepared alpha6 integrin-specific mAb MA6 bound to an epitope in close proximity to GoH3, but it had no effect on VLA-6-mediated cell adhesion. We report here that although MA6 did not affect adhesion, it blocked mouse melanoma B16F1 cell movement on laminin to the same extent as GoH3. Results therefore demonstrate an active role of VLA-6 in providing cell movement as well as the initial adhesive event on laminin. In addition, mAb MA6 had no effect on the induction of tyrosine phosphorylation of focal adhesion kinase upon adhesion of B16F1 cells to laminin. Therefore, inhibition of cell movement by MA6 involved mechanism(s) other than an interference of VLA-6 signaling events leading to phosphorylation of focal adhesion kinase. The epitopes of GoH3 and MA6 may represent spatially and temporally related sites on VLA-6 that are involved during cell movement, or, alternatively, MA6 may inhibit the interaction of VLA-6 with associated cell surface molecules required for cell movement. In vivo videomicroscopy experiments also revealed that an inhibition of VLA-6 migratory function by MA6 resulted in a reduction in the ability of B16F1 to extravasate during hematogenous metastasis in the liver.
Cancer Res 1997 Sep 01
PMID:An epitope on VLA-6 (alpha6beta1) integrin involved in migration but not adhesion is required for extravasation of murine melanoma B16F1 cells in liver. 928 92

Mel-cell adhesion molecule (CAM), also known as MUC18 and CD146, is a novel member of the immunoglobulin supergene family. Mel-CAM was first identified as an integral membrane glycoprotein in human melanoma and is also abundantly expressed by endothelial cells of various origins. In a previous study (I. M. Shih et al., Cancer Res., 54: 2514-2520, 1994), we showed that Mel-CAM is a cell-cell adhesion molecule with a possible role in melanoma invasion and metastasis. Here, we define the molecular mechanism responsible for cell-cell adhesion of Mel-CAM and demonstrate its role in melanoma-endothelial cell interactions. Most of human melanoma cells, including Mel-CAM-negative SBcl-2 cells, adhered to nitrocellulose-immobilized Mel-CAM produced by baculovirus recombinants. This adhesion can be blocked by full-length Mel-CAM or polyclonal antiserum against Mel-CAM. Adhesion is not affected by the presence of EDTA, truncated Mel-CAM extracellular domain, or heparan sulfate proteoglycan. In cell aggregation assays, Mel-CAM-negative SBcl-2 cells cluster with U937TM cells (U937 transfected with Mel-CAM cDNA) but not with control nontransfectants, suggesting that SBcl-2 cells express the ligand for Mel-CAM. SBcl-2 cells also form heterotypic aggregates with Mel-CAM-positive human endothelial cells but not with Mel-CAM-negative but ligand-positive smooth muscle cells. Taken together, our results show that Mel-CAM mediates cell-cell adhesion through heterophilic adhesion to an as yet unidentified ligand present on melanoma but not on endothelial cells. Thus, melanoma-endothelial interactions during metastasis may occur through this novel mechanism.
Cancer Res 1997 Sep 01
PMID:Melanoma cell-cell interactions are mediated through heterophilic Mel-CAM/ligand adhesion. 928 96

We have examined the functional status of the VLA-4/alpha4beta1 integrin in a panel of human melanoma cell lines, focusing on the ability of cells expressing alpha4beta1 to mediate adhesion to the alpha4-specific ligands CS-1 peptide and VCAM-1. All melanoma cells expressing alpha4pbeta1 (8 of 10 lines examined) were capable of adhering to these specific ligands in adhesion assays, whereas 2 cell lines (HMB2 and VUP) which lacked surface alpha4 were unable to do so. Adherence of different melanoma cell lines to VCAM-1 was relatively uniform and not susceptible to upregulation with known integrin-activating factors, such as manganese ions, phorbol ester and activating monoclonal antibody (mAb) TS2/16. Cell adhesion to CS-1 peptide, however, varied according to cell surface receptor density and, in some cases, could be up-regulated by integrin-activating factors. Adhesion of SK23 cells to CS-1 peptide was increased by all 3 activating stimuli, whereas for all other melanoma cells an increase was obtained only by the use of TS2/16 mAb. Our data indicate not only an unusually low activation state of alpha4beta1 in SK23 cells but also heterogeneity in the activating capacity of the various stimuli. Moreover, a protein kinase C-dependent role in alpha4beta1 activity was suggested by adhesion assays carried out in the presence of the protein kinase C inhibitor calphostin C, which considerably reduced adhesion to CS-1 peptide.
Int J Cancer 1997 Oct 09
PMID:Activation status and function of the VLA-4 (alpha4beta1) integrin expressed on human melanoma cell lines. 933 53

Evidence is mounting that changes in the ability of cancer cells to adhere to extracellular matrices play a decisive role in metastatic spread. The mechanism underlying the preference of breast cancer cells to metastasize to bone is, however, poorly understood. We investigated the expression and involvement of integrin adhesion receptors in the adhesion of breast cancer cells to bone matrix (constituents) in two in vitro attachment assays using RGD peptides and anti-integrin antibodies. Breast cancer cells adhered rapidly to extracellular bone matrix. Adhesion of most cells to vitronectin, fibronectin, thrombospondin, osteopontin, and the fairly bone-specific bone sialoprotein was inhibited by the 200 micrograms/ml GRGDS peptide. These data suggest that integrin adhesion receptors can modulate the attachment of breast cancer cells to bone matrix molecules. In accordance with these findings, we found that alpha 1-alpha 5(beta 1) and alpha v(beta 3) integrins were expressed by mammary carcinoma cells. Highly tumorigenic MDA-MB-231 cells, which form osteolytic metastases in vivo, expressed relatively high levels of alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 3 integrins, when compared to MCF-7, T47D, and ZR75-1 breast cancer cells. Addition of function-blocking anti-alpha 2 beta 1, -alpha 3 beta 1, -alpha 5 beta 1, and -alpha v beta 3 antibodies significantly inhibited the adhesion of MDA-MB-231 breast cancer cells to bone matrices. In conclusion, our data suggest a possible role for beta 1 and beta 3 integrin subfamily members in the establishment of skeletal metastases in advanced breast cancer patients. Clearly, functional evidence is required to understand the mechanisms involved in the development of skeletal metastases in breast cancer patients.
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PMID:Attachment characteristics and involvement of integrins in adhesion of breast cancer cell lines to extracellular bone matrix components. 942 5

Adhesion molecules play a major role in the processes of invasion and metastasis of malignant tumors. Their expression within tumors has been reported to be quantitatively and qualitatively altered according to the invasiveness and metastatic potential of the tumor. The present study tested whether the intratumoral expression of integrin alpha 3 can be detected by a radiolabeled monoclonal antibody. The in vitro binding study with four different human cancer cells showed that radioiodinated GA17 antibody recognizing integrin alpha 3 bound specifically to these cells to varying degrees, according to the antigen density on each cell. The biodistribution study with 125I- and 111In-labeled antibodies showed specific localization of radiolabeled GA17 to the xenografts. However, the in vivo tumor localization was not proportional to the antigen density calculated in vitro, and antibody metabolism varied among the tumors, as was also confirmed by in vitro radionuclide retention assay. The intratumoral distribution of radioactivities varied reflecting the antigen expression within the tumor. These results indicate that 1) integrin alpha 3 was expressed in various kinds of tumors and could be localized by the radiolabeled antibody, and 2) the expression of integrin alpha 3 and the metabolism of the radiolabeled antibody after binding to the antigen within the tumor were variable among the tumors, which affected the radionuclide distribution characteristics. The expression of adhesion molecules within these tumors was noninvasively detected by a radiolabeled antibody. It may be possible to use integrin alpha 3, when it is overexpressed, as a target of therapy with antibodies radiolabeled with alpha or beta emitters.
Jpn J Cancer Res 1997 Dec
PMID:Detection of altered adhesion molecule expression in experimental tumors by a radiolabeled monoclonal antibody. 947 35

Adhesion molecules might play a role in tumor progression. We investigated expression of the adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in 24 primary colorectal carcinomas using immuno-histochemistry and Northern blot analysis. Normal colonic tissue from the same patients served as controls. ICAM-1 immunostaining was restricted to the intercellular matrix and vascular endothelial cells. The vast majority of normal tissue samples revealed only faint ICAM-1 immunoreactivity. However, moderate to strong immunostaining was found in 86% of cancerous sections. The ICAM-1 immunoreaction was more intense in well-differentiated carcinomas as well as in the adenomatous parts and transition zones of cancers. Similarly, the cancers exhibited markedly enhanced VCAM-1 and ELAM-1 immunostaining in the endothelial cells of small blood vessels. The intense vascular immunostaining by ICAM-1 and VCAM-1 was associated with a strong presence of CD3-positive T lymphocytes, whereas ELAM-1 immunoreactivity did not correlate with round cell infiltration. On Northern blot analysis, ICAM-1, VCAM-1 and ELAM-1 mRNA levels were increased in 67%, 57% and 63% of carcinomas, respectively, in comparison with normal tissue samples. Densitometric analysis of Northern blots revealed an increase in ICAM-1 by 2.1-fold, an increase in VCAM-1 by 3.4-fold and an increase in ELAM-1 by 2.2-fold in cancerous tissues compared to normal controls. Over-expression of ICAM-I might prevent cell-cell disruption and, hence, tumor dissemination. Furthermore, over-expression of ICAM-1 and VCAM-1, but not ELAM-1, might favor host anti-tumor defense by trafficking of lymphocytes.
Int J Cancer 1998 Feb 20
PMID:Over-expression of ICAM-1, VCAM-1 and ELAM-1 might influence tumor progression in colorectal cancer. 949 63

We have investigated the effects of laminin, on the plasminogen-activator system of MCF-7 breast-carcinoma cells. MCF-7 cells were incubated on plastic or laminin-coated wells, and medium and cell lysate aliquots were assayed for tissue-type (tPA) and urokinase-type plasminogen activator (uPA) by a chromogenic assay in combination with anti-uPA antibodies. Cells cultured on laminin displayed a 5-fold increase in tPA activity and a 2-fold decrease in uPA activity relative to cells on plastic. These effects could be mimicked by laminin fragment P1 but not by collagen I or fibronectin. tPA activity of cells treated with estradiol (10 nM) was 3-fold higher, that of cells on laminin treated with estradiol was 15-fold higher, than that of control. Northern-blot analysis showed that tPA mRNA levels were up-regulated by estradiol and laminin, whereas PAI-1 mRNA levels were down-regulated by laminin and not affected by E2. Concomitant treatment with laminin and estradiol, decreased PAI-1 mRNA and increased tPA mRNA levels, accounting for the synergistic increase in tPA activity. Laminin exerted only a modest (approx. 2-fold) inhibitory effect on uPA mRNA levels. In the breast-carcinoma cell line MDA-MB-231, down-regulation of PAI-1 and uPA mRNA by laminin was not observed. Adhesion assays indicated that alpha2beta1 is the predominant receptor for laminin in MCF-7 cells. MDA-MB-231 cells expressed alpha2 (54%) but this integrin is not used as a laminin receptor. These results support a role for alpha2beta1 in mediating interactions of MCF-7 with LN.
Int J Cancer 1998 Mar 30
PMID:Laminin and estradiol regulation of the plasminogen-activator system in MCF-7 breast-carcinoma cells. 953 65

Alpha(1,3)- and alpha(1,4)-fucosylated oligosaccharides such as sialyl-Lewis(x) (sialyl-Le(x)) and sialyl-Lewis(a) (sialyl-Le(a)) have been reported to participate in tumor cell adhesion to activated endothelium. We examined by cytofluorometry the expression of Le(x), sialyl-Le(x), sialyl-Le(x) dimeric, Le(a), and sialyl-Le(a) on the surface of two human lung adenocarcinoma cell lines with different lung colonization potential. High expression levels of all of these antigens were detected in the metastatic HAL-8Luc cells, whereas the closely related nonmetastatic HAL-24Luc cells only expressed the sialyl-Le(a) and sialyl-Le(x) dimeric antigens, both at lower level than in HAL-8Luc cells. Five alpha(1,3)-fucosyltransferases (alpha(1,3)-Fuc-T) controlling the synthesis of these molecules have been identified to date (Fuc-TIII-Fuc-IVII). The expression of these five genes was also higher in the metastatic cells than in the nonmetastatic counterparts as was shown by Northern blot analysis. In vitro adhesion assays showed that only the metastatic cell line adheres significantly to E-selectin-expressing human endothelial cells. Moreover, monoclonal antibody (mAb) blockade of E-selectin completely abolished tumor cell binding. Adhesion inhibition experiments using mAbs against sialylated fucosylated oligosaccharides expressed on tumor cells indicated that these antigens are involved in the binding. Anti-sialyl-Lex(x) mAb (CSLEX-1) inhibited adhesion by 85%; it had the most pronounced inhibitory effect. These findings suggest that the overexpression of alpha(1,3)-Fuc-T genes in the metastatic HAL-8Luc cells, compared with HAL-24Luc cells, results in an enhanced surface display of fucosylated oligosaccharides, which contributes to the adhesive capacity of these cells to the activated endothelium and correlates with their lung colonization potential.
Cancer Res 1998 Apr 01
PMID:Enhanced expression of alpha(1,3)-fucosyltransferase genes correlates with E-selectin-mediated adhesion and metastatic potential of human lung adenocarcinoma cells. 953 62

We investigated alterations in the expression of integrin on adriamycin-resistant MCF-7 (MCF-7/ADR) cells, which had been selected from MCF-7 human breast cancer cells, in order to examine the mechanisms behind the acquisition of malignancy in breast cancer progression. Expression of the alpha 6 integrin subunit of MCF-7/ADR cells was stronger than that of MCF-7 cells, whereas expression of alpha 2 integrin subunit of MCF-7/ADR cells was weaker than that of MCF-7 cells. MCF-7/ADR showed increased binding activity to laminin, but not to collagen or fibronectin, compared to those of parental MCF-7 cells. Adhesion of MCF-7 cells to collagen and laminin was inhibited by the addition of antibody to alpha 2 and alpha 6 integrin subunit, respectively. On the other hand, adhesion of MCF-7/ADR cells to collagen was not inhibited by the addition of antibody to alpha 2, alpha 3 or alpha 6 integrin subunit. Adhesion of MCF-7/ADR cells to laminin was inhibited by not only the antibody to alpha 6 subunit but also the antibody to the alpha 3 subunit. The transmigratory activity of MCF-7/ADR cells was higher than that of MCF-7 cells. A significant inhibitory effect on the transmigration of MCF-7/ADR cells was observed by the addition of antibody to alpha 6 and beta 1 integrin subunit. MCF-7/ADR cells appeared smaller and flatter than MCF-7 cells, and spread to a greater extent on the culture dish. MCF-7 cells cultured on Matrigel for 24 hours formed clusters. In contrast to this, MCF-7/ADR cells expanded with a tubular-like pattern on Matrigel. The spread of MCF-7/ADR cells was incompletely inhibited by addition of the antibody to alpha 3 integrin subunit, and completely inhibited by addition of the antibody to alpha 6 and beta 1 integrin subunit. These findings suggest that integrins on MCF-7/ADR cells are altered from those on parental MCF-7 cells in not only expression but also function, and that interaction between cancer cells and extracellular matrix protein is involved in augmentation of the invasiveness of MCF-7/ADR cells.
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PMID:Altered expression of integrins in adriamycin-resistant human breast cancer cells. 956 87

Two breast cancer cell lines, YMB-S and ZR-75-1S, were established in our laboratory. They proliferated in suspension culture without aggregation in a complete liquid medium. We found that sodium butyrate (NaB) arrested the cells in the G0-G1 phase of the cell cycle, inhibited their proliferation, and induced cell-cell and cell-surface adhesion. In this study, we explored the mechanism of this adhesion. Adhesion was inhibited by an anti-E-cadherin antibody, suggesting a role for E-cadherin. However, there were no changes in the expression of E-cadherin, alpha-catenin, and beta-catenin. Northern blot analysis and cytofluorometry revealed that NaB-treated cells showed a lower expression of MUC1 than did untreated cells. To examine the possibility that the adhesion of these cells might be induced by decreased MUC1 expression, the level of MUCI expression was directly reduced using an antisense oligonucleotide. The MUC1 antisense oligonucleotide induced cell-cell and cell-surface adhesion of these breast cancer cells, just as NaB did. Our observations indicate that E-cadherin can be functionally suppressed by overexpression of MUC1 but resumes its activity after suppression of MUC1 expression. Thus, regulation of MUC1 might be a new strategy for cancer therapy.
Cancer Res 1998 May 01
PMID:Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast cancer cell lines. 958 47


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