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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Invasion is the hallmark of tumor malignancy. We situate invasion within microecosystems comprising neoplastic cells as well as host cells. Modulation of invasion within such systems is ascribed to balances between promoter and suppressor pathways. The E-cadherin/alpha-, beta-, gamma-catenin complex has an invasion-suppressor function as evidenced by transfections either with sense cDNA encoding these molecules or with antisense cDNA inhibiting their expression. Loss of heterozygosity at the E-Cadherin (uvo) locus has been reported, but mutations in the E-cadherin gene seem to be rare. Downregulation of E-cadherin occurred at the level of transcription or of mRNA stability. Ex vivo cultures from invasive tumors or metastases produced cells that were homogeneously E-cadherin-positive and noninvasive in vitro. These observations have led to the idea that factors in the host downmodulate the E-cadherin complex and promote invasion most probably in a transient way.
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PMID:Cancer metastasis: negative regulation by an invasion-suppressor complex. 758 33

We examined the expression and ligand specificity of the alpha 2 beta 1 integrin on human mammary epithelial cells (HMEC) and a panel of breast carcinoma cell lines in vitro. We found that the alpha 2 beta 1 integrin was universally, but quite variably expressed on these cells by FACS analysis. No significant correlation was observed between its expression and other known cellular phenotypes. Substrate attachment assays using blocking antibodies demonstrated that alpha 2 beta 1 integrin served as a receptor for collagen on HMEC and almost all breast carcinoma cells. However, its contribution to laminin binding of these cells appeared to be related to cellular differentiation as evaluated by sex steroid receptor status and by markers of epithelial-mesenchymal transition, i.e. loss of E-cadherin and expression of vimentin. Two different populations of non-malignant immortalized HMEC (184A1N4 and MCF-10A) contained cells capable of using alpha 2 beta 1 integrin as a laminin receptor. Breast cancer cell lines positive for estrogen receptor (ER) and E-cadherin (MCF-7, T47D, ZR75-1) could also use alpha 2 beta 1 integrin as a laminin receptor. Conversely, alpha 2 beta 1 integrin appeared to be incapable of binding to laminin or to be a very minor receptor for laminin on metastatic ER-negative breast carcinoma cells that expressed vimentin (MDA-MB 231, MDA-MB 435, and MDA-MB 436). These findings suggest that the ligand specificity of alpha 2 beta 1 integrin, i.e. its function as a laminin receptor, may be regulated during the malignant progression of breast carcinoma cells. A reduced contribution of alpha 2 beta 1 integrin to the cellular laminin binding appears to be associated with an increased malignant phenotype and with an epithelial-mesenchymal transition of breast carcinoma cells.
Clin Exp Metastasis 1995 Jul
PMID:Expression and ligand binding of alpha 2 beta 1 integrin on breast carcinoma cells. 760 85

The aim of this study was to evaluate the expression of E-cadherin as a potential marker for the prognosis of thyroid carcinomas. In normal thyroid (n = 8), the expression of E-cadherin messenger ribonucleic acid levels was uniformly high and seemed to be restricted to thyrocytes. Steady-state messenger ribonucleic acid levels and immunostaining were both completely lost in undifferentiated thyroid carcinomas (n = 7) and were variably reduced in differentiated thyroid carcinomas (n = 44). In a follow-up study during a mean of 4.5 +/- 1.4 yr, E-cadherin messenger ribonucleic acid and immunohistochemical expression were compared with the initial clinicopathological parameters and with locoregional recurrence and the development of nodal or distant metastases in differentiated thyroid carcinomas. Immunohistochemical expression of E-cadherin was greatly reduced with the progression to primary tumor stage 4 (pT4) tumors. In parallel, patients with pT4 tumors had a higher rate of locoregional tumor recurrence and distant metastasis than did the group of patients with pT1-3 tumors. In 5 of 29 patients with pT4 tumors, positive E-cadherin staining of more than 30% of the cells was detected. None of these patients showed signs of a regional recurrence or distant metastases during an observation period of 4.3 +/- 1.1 yr. In 13 patients with E-cadherin-positive tumors, none developed new distant metastases which was in contrast to 7 of the group of 31 patients with less than 30% E-cadherin-positive cells. Thus, E-cadherin expression seems to be associated with the dedifferentiation, progression, and metastatic spread of thyroid carcinomas and may be a useful marker for the prognosis of these tumors.
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PMID:Clinical significance of E-cadherin as a prognostic marker in thyroid carcinomas. 760 73

Metastasis of colon carcinomas is assumed to be caused by multiple steps, which include a loss of cell adhesion that results in the release of carcinoma cells from the original tumor tissue. A human colon carcinoma cell line was established from a poorly differentiated metastatic adenocarcinoma without cell-cell adhesion and without expression of E-cadherin mRNA. To this cell line, mouse E-cadherin cDNA in a expression vector was co-transfected with a neomycin-resistant gene. The transfected cells, which expressed exogenous E-cadherin gene, showed a compact shape with strong cell-cell adhesion and with increased cell-substratum adhesion. These cells showed a significantly low anchorage independency and decreased invasiveness compared to the parental carcinoma cells. Their growth rate was decreased both in vitro and in the subcutis of nude mice.
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PMID:[Increased cell adhesiveness and decreased tumorigenicity induced in human colon carcinoma cells by transfection with E-cadherin cDNA]. 762 92

We examined expression of E-cadherin cell-cell adhesion molecule, which is supposed to have invasion-suppressing activity, in 53 cases with endometrial carcinoma. Fresh frozen sections were immunostained with a mouse monoclonal antibody to human E-cadherin (HECD-1). E-cadherin expression was inversely correlated with grade of tumor (p = 0.0267), depth of myometrial invasion (p = 0.0146) and pelvic and paraaortic node metastases (p = 0.0184 and p = 0.0419, respectively). Multivariate analysis revealed that among histologic grade, nuclear grade, and E-cadherin expression, E-cadherin expression was most strongly correlated with depth of myometrial invasion (p = 0.0491). These results suggest that decreased expression of E-cadherin facilitates invasion of endometrial carcinoma.
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PMID:[Abnormal E-cadherin expression as a risk factor for deep myometrial invasion and lymph node metastasis in endometrial carcinoma]. 762 96

HECD-1 monoclonal antibody has been used to localize E-cadherin, a calcium-dependent cell-cell adhesion molecule, in microwave-treated, paraffin-embedded sections from 53 cases of cervical intraepithelial neoplasia (CIN) (11 CIN I, 22 CIN II, and 20 CIN III), 16 invasive cervical squamous cell carcinomas, and seven metastases. In normal cervix, E-cadherin was expressed on the cell membrane of basal and parabasal cells. Cytoplasmic staining was present in occasional basal cells only. In CIN, the presence and localization of cytoplasmic E-cadherin were found to be significantly correlated with the grade of the CIN lesion. In squamous cell carcinomas, reduced membranous and increased cytoplasmic staining was seen with worsening differentiation. Loss of membranous E-cadherin expression was also detected in 4/7 metastatic deposits. E-cadherin expression (120 kD form on Western blotting) was seen in human cervical carcinoma cell lines (HT3, ME180, C4I, Caski) that maintained the ability to aggregate in a homotypic adhesion assay and showed a typical epithelial morphology. E-cadherin-negative cell lines (Hela, SiHa, C33A) did not show adhesion. HOG-1 was the only E-cadherin-negative cell line which showed a significant degree of cell-cell aggregation. These data indicate that loss of membranous E-cadherin expression may represent one of the abnormalities underlying loss of cell polarity and differentiation which characterize CIN and invasive cervical cancer.
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PMID:Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma. 763 25

Tumour cell motility and attachment are crucial requirements in the formation of metastatic lesions. These properties are affected by a number of cytokines including hepatocyte growth factor/scatter factor (HGF/SF) and several immunoregulatory proteins, including interleukin-12 (IL-12). Although IL-12 has been reported to exhibit potent anti-tumour effects in vivo, a direct effect of IL-12 on cancer cells has not been reported. We show here that IL-12 directly inhibited the attachment of the human colon cancer cell lines HRT18, HT29 and HT115 to Matrigel, HGF/SF-stimulated cell motility and HGF/SF-induced cell invasion through a reconstituted basement membrane. IL-12 did not affect the growth of these cell lines. Flow cytometry, Western analysis and immunohistochemistry revealed an up-regulation of E-cadherin cell-surface adhesion molecules. These direct effects of IL-12 on colon cancer cells suggest a potentially important role for IL-12 in metastasis.
Clin Exp Metastasis 1995 Sep
PMID:Inhibition of cancer cell motility and invasion by interleukin-12. 764 24

Melanoma often develops from clinically and histologically well-defined precursor lesions. During progression of normal melanocytes to benign nevi, dramatic changes in the expression of adhesion receptors are observed, most notably loss of E-cadherin which mediates adhesion of melanocytes to keratinocytes, and gain of Mel-CAM which predominantly mediates heterotypic adhesion between cells. Major changes in adhesion receptors also occur when cells progress from dysplastic nevi or biologically early radial-growth-phase primary melanomas to biologically late (tumorigenic) vertical-growth-phase primary melanomas. The integrin subunit beta 3 is up-regulated, whereas other integrins such as alpha 6 beta 1 and alpha V beta 1 are down-regulated. This review highlights the major changes in adhesion receptor expression on melanocytes at various stages of tumor progression.
Invasion Metastasis
PMID:Adhesion receptors in human melanoma progression. 765 8

Histotypic differentiation and prognosis of carcinomas are intimately linked phemonena, i.e. poorly differentiated tumors show increased invasiveness and have a worse prognosis compared to well-differentiated tumors. In poorly differentiated carcinomas, loss of epithelial cell contacts is frequently observed; this allows the cells to break away from the primary tumor and invade surrounding tissue. The molecular basis for the disturbance of epithelial junction formation in tumors has been the subject of recent research. It has become clear that the epithelial cell adhesion molecule E-cadherin and its associated proteins, the catenins, are of central importance for the establishment of the epithelial phenotype and the prevention of invasiveness, and that aberrations in these components contribute to metastasis. The molecular mechanisms controlling the E-cadherin-based adhesion system in normal epithelial cells and in invasive carcinomas are the topic of this review.
Invasion Metastasis
PMID:Cell contacts, differentiation, and invasiveness of epithelial cells. 765 33

The ultimate stage of carcinogenesis in both human and mouse epithelial cells is the ability to invade surrounding tissues and metastasize to distant sites. In mouse skin tumours, the development of the invasive, spindle cell phenotype is associated with an imbalance of alleles on mouse chromosome 7, including the H-ras gene. In previous work, we have described clonally related squamous and spindle cell lines from the same primary tumour which differed substantially in morphology and behaviour, but showed the same series of mutations in H-ras and p53 genes. One of the events which takes place during this transition is disruption of cell-cell contacts, possibly due to the induced expression of metalloproteinases such as stromelysin-1 and disappearance of the cell adhesion molecule E-cadherin. Parallel studies using somatic cell hybrids have shown that the spindle cell phenotype is recessive in hybrids between squamous and spindle cells. We propose that an important epidermal differentiation-controlling gene is lost during the spindle cell transition.
Invasion Metastasis
PMID:Molecular mechanisms of invasion and metastasis during mouse skin tumour progression. 765 34


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