Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-MET proto-oncogene encodes the receptor for the Hepatocyte Growth Factor/Scatter Factor, which is known to mediate mitogenic, motogenic and invasive responses of several cell types. We have analysed by immunohistochemistry and biochemically the expression of c-MET in benign and malignant melanocytic lesions. The Met/HGF receptor which in the melanocytic lineage displays the structural features of the authentic receptor was undetectable in tissue melanocytes and in nevocytic nevi. Only four out of 23 primary melanomas scored positive. Expression was increased to a significant level in 17 out of the 44 metastatic lesions examined. The c-MET expression was homogeneous in multiple metastases from the same patients. Comparative analyses showed both lack of correlation with the expression of the tumour progression associated ICAM-1 adhesion molecule and, in 23% of cases, co-expression with the c-KIT encoded receptor. These findings show that the c-MET gene is expressed at late stages of melanoma progression and suggest that the presence of Met/HGF receptor may contribute to the acquisition of an invasive phenotype.
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PMID:Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression. 810 62

Down-regulation of E-cadherin, an intercellular adhesion molecule, and up-regulation of autocrine motility factor receptor (gp78) expressions have been shown to play a role in tumor cell invasion and metastasis. Monoclonal antibodies against E-cadherin and gp78 were used to stain serial snap-frozen sections of 12 normal bladder and 83 bladder carcinoma specimens (27 noninvasive, 53 invasive, and 3 metastases). In normal urothelium, E-cadherin is expressed while gp78 is not. Positive expression of E-cadherin and negative expression of gp78 were found to be associated with a low risk of clinical progression in the superficial bladder carcinoma patient group. While reduction in E-cadherin concomitantly with an increase in gp78 expression was associated with poor prognosis, 71% of the patients (n = 30) underwent rapid cancer progression, and 32% of the patients died of cancer-related disease at a median of 2 years after initial diagnosis. Thus, it is suggested that reduction of E-cadherin expression associated with an increase in the level of gp78 in bladder cancers may define a high risk group of patients. The dual use of these two antigens may improve early diagnosis of high risk bladder cancer patients and influence treatment decisions.
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PMID:Inverse relation of E-cadherin and autocrine motility factor receptor expression as a prognostic factor in patients with bladder carcinomas. 820 27

Normal lung epithelium and 52 lung carcinomas obtained at surgical resection were examined by immunofluorescence for their expression levels and patterns of the calcium-dependent intercellular adhesion molecule E-cadherin. In dysplastic lung tissue and in well-differentiated squamous cell and adenocarcinomas, expression of E-cadherin was confined to the lateral cell border, similar to the expression level and pattern of normal lung tissue. The E-cadherin level was reduced and expression pattern was spotty or diffuse in moderately and poorly differentiated squamous cell and in small cell carcinomas of the lung. Most metastases resected also had a reduced level and an altered pattern of E-cadherin expression. In contrast, no such correlation was found in adenocarcinomas of the lung. This indicates that different cellular mechanisms are responsible in the progression of squamous cell carcinomas and adenocarcinomas of the lung.
Clin Exp Metastasis 1994 Jan
PMID:Differences of E-cadherin expression levels and patterns in primary and metastatic human lung cancer. 828 21

Retinoic acid (RA) is a potent inhibitor of the malignant phenotype and of tumour cell growth. We observed that in vitro RA treatment of a highly metastatic lung carcinoma cell line (C87) induced a marked reduction in the amount of the beta 4 integrin subunit. The downregulation of this adhesion molecule was assessed by immunofluorescence, immunoprecipitation, and northern analysis. In order to investigate the effects of RA on the malignant phenotype in C87 cells we performed morphological and functional analysis after RA treatment. We found that RA was able to produce marked changes in C87 cell shape, increasing the number of flat cells (90% of the total cell population), and significantly inhibiting the malignant and invasive phenotype of C87 cells. RA treatment suppressed their clonogenic potential in soft agar (control, 20 +/- 5; RA, 0), and strongly reduced their chemotactic and chemoinvasive capacity (chemotaxis: control, 231 +/- 5; RA, 28 +/- 0; chemoinvasion: control, 132 +/- 11; RA = 2 +/- 1). FACS analysis and cell count, however, indicated that RA reduced the growth of C87 cells only partially. After 72 h of treatment we observed only a 10% reduction in the S phase fraction of the cell population. Finally, the reduced lung colony-forming ability, observed after i.v. injection of RA-treated cells (lung foci/animal: RA-treated cells, 1 +/- 0.1; untreated, 8.5 +/- 0.8), further supports the conclusion that in this murine lung carcinoma cell line a marked reduction in the expression of the beta 4 integrin subunit is associated with a marked inhibition of the malignant phenotype.
Clin Exp Metastasis 1994 Jan
PMID:Retinoic acid negatively regulates beta 4 integrin expression and suppresses the malignant phenotype in a Lewis lung carcinoma cell line. 828 22

Ever since it was discovered that CEA, as member of the CEA-gene family, is part also of the Ig-supergene family, to which molecules involved in cell interactions like cell adhesion or cell recognition belong, great efforts were made to prove that CEA is also an adhesion molecule. At present this seems to be an accepted fact. In the present study we advance a different theory which is based on the expression pattern of CEA during ontogeny and in malignancy and which is suggestive of CEA functioning more as a signal protein prohibiting further cell/cell contact rather than as an adhesion molecule. In the malignant state the expression of this molecule on the surface of tumor cells would facilitate migration and motility, i.e., metastases formation. Furthermore it would prevent a tight contact between cytotoxic effector cells and CEA expressing target cells.
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PMID:Possible function of CEA as cell-contact inhibitory molecule. 857 74

It has been shown that isoforms of the adhesion molecule CD44 are involved in the metastatic spread of several human malignancies. To determine whether CD44 plays a role in metastasis of human ovarian cancer, the tumours and corresponding metastases of 28 patients were investigated. CD44 was detected by immunohistochemistry in 2 primary tumours (7.1%) and 3 metastases (10.7%). In no case did both the primary tumour and metastasis show CD44 expression simultaneously. The results presented here suggest that CD44 does not play a crucial role in the metastatic spread of human ovarian cancer.
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PMID:CD-44 is not involved in the metastatic spread of ovarian cancer in vivo. 866 61

Prostacyclins have long been shown to have anti-metastatic activity. One hypothesis is their modulation of cell adhesion molecule (CAM) expression by target organ endothelial cells. We have postulated that prostacyclin, its analogs, and mechanistic mimics decrease colon carcinoma adhesion to cytokine-stimulated endothelial cells by blocking endothelial expression of the adhesion molecule E-selectin, but not the vascular cell adhesion molecule-1 (VCAM-1). Cultured human microvascular endothelial cells (HDMEC) were pre-incubated with prostacyclin (PGI2), dibutyrl-cAMP (dbcAMP), forskolin (FOR), and/or iso-methylbutylxanthine (IBMX) for 15 min, then co-incubated with the cytokine tumor necrosis factor (TNF) for 4 h. HDMEC surface expression of E-selectin and VCAM-1 was evaluated by flow cytometry and ELISA. Adherence of 51Cr-labeled colon carcinoma cells to HDMEC monolayers was then determined. In parallel assays, HDMECs were incubated with anti-E-selectin and anti-VCAM-1 monoclonal antibody (1:100) prior to the addition of tumor cells. Prostacyclins, its analogs, and mimics significantly reduced E-selectin expression by HDMEC, while the reduction of VCAM-1 expression was much less pronounced. Prostacyclins also significantly decreased colon carcinoma adherence to stimulated HDMECs. The inhibition of E-selectin expression, but not VCAM-1 expression, corresponded to the reduction of tumor cell adherence. Prostacyclin's effects on tumor adhesion were nullified by pre-incubation with E-selectin antibody. The inhibition of colon carcinoma adherence to cytokine-stimulated endothelial cells treated with prostacyclin, its analogs, and mimics appears to result from blocking endothelial E-selectin, but not VCAM-1, expression. These data support the hypothesis that prostacyclins may exert their anti-metastatic effect, in part, by inhibiting CAM-mediated adherence of colon carcinoma to endothelial cells in metastatic target organs.
Clin Exp Metastasis 1996 May
PMID:Anti-metastatic prostacyclins inhibit the adhesion of colon carcinoma to endothelial cells by blocking E-selectin expression. 867 77

Epithelial ovarian carcinoma, the leading cause of gynecologic cancer death, is characterized by widespread intra-abdominal metastases mediated primarily by surface shedding of tumor cells and peritoneal implantation. Whereas hematogenous metastasis is known to involve cellular adhesion, extracellular matrix proteolysis and cell migration, the role of these processes in the intraperitoneal dissemination of ovarian cancer remains unclear. To analyze further the role of adhesion and proteolysis in ovarian carcinoma dissemination, we have characterized the adhesive profiles of 4 primary cultures of ovarian carcinoma cells and 5 ovarian carcinoma cell lines. Our data demonstrate preferential adhesion of ovarian carcinoma cells to interstitial type I collagen. Analysis of adhesion molecule expression demonstrated the presence of the alpha2 and beta1 integrin subunits by cell surface ELISA, immunoprecipitation and immunohistochemistry. Furthermore, antibodies directed against the alpha2 and beta1 subunits inhibited adhesion of ovarian carcinoma cells to type I collagen by 56% and 95%, respectively. Plasminogen activator and matrix metalloproteinase production by adherent cells was not altered as a consequence of adhesion to individual extracellular matrix proteins; however, adhesion to an extracellular matrix comprised primarily of interstitial collagen increased plasminogen activator activity in 5 of 5 cell lines. Since the ovarian carcinoma micro-environment is rich in type I collagen, our data suggest that preferential adhesion to type I collagen followed by secretion of serine and metalloproteinases may represent a biochemical mechanism by which the intraperitoneal dissemination of ovarian carcinoma is mediated.
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PMID:Evidence for preferential adhesion of ovarian epithelial carcinoma cells to type I collagen mediated by the alpha2beta1 integrin. 878 61

To evaluate the role of affinity in monoclonal antibody (mAb)-mediated treatment of carcinomas, we compared the antibodies 17-1A and 323/A3 that bind with different affinities overlapping epitopes on the epithelial adhesion molecule Ep-CAM. This comparison was performed in several models for minimal residual disease in mice grafted with Ep-CAM transfected B16 melanoma cells originating from C57BL/6 mice. These cells were either grafted subcutaneously or injected intravenously into nude BALB/c mice, or grafted subcutaneously in immunocompetent C57BL/6 mice. In the BALB/c subcutaneous model, significant therapeutic results (p < 0.05) compared with the control mAb were obtained with both mAbs 17-1A and 323/A3. However, when treating lung metastases in nude BALB/c mice that had developed after intravenous injection of the B16/Ep-CAM tumor cells, only the high-affinity 323/A3 mAb could significantly (p < 0.05) reduce the number of metastases that appeared. In syngeneic C57BL/6 mice grafted subcutaneously with B16/ Ep-CAM cells, a single 323/A3 or 17-1A mAb injection had no effect, in contrast to that observed for the nude BALB/c mouse model. However, multiple injections of the 323/A3 mAb significantly (p < 0.005) reduced the mean tumor volume, although they did not prevent tumor development. The results show that in vivo antibody-mediated effector cell activation and subsequent tumor cell elimination is determined by mAb affinity and target antigen density. Therefore, treatment of minimal residual disease with high-affinity mAb 323/ A3 is expected to improve the clinical results obtained with mAb 17-1A.
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PMID:The role of monoclonal antibody affinity in tumor immunotherapy evaluated in in vivo models for minimal residual disease. 887 19

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.
Clin Exp Metastasis 1996 Sep
PMID:Human ovarian tumour cells can bind hyaluronic acid via membrane CD44: a possible step in peritoneal metastasis. 887 6


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