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

Enhanced expression of the epidermal growth factor receptor and loss of expression of the cell-cell adhesion molecule E-cadherin have each been implicated in the development and progression of a variety of human malignancies. There is some evidence for a correlation between the expression of these two genes and the possible influence of the E-cadherin gene product on the expression of epidermal growth factor receptor. We evaluated 33 matched primary and metastatic non-small cell lung cancer specimens using immunohistochemical staining. There was a statistically significant correlation between staining intensity for epidermal growth factor receptor and E-cadherin in the primary tumors (P = 0.017, by Spearman correlation test). No difference was noted between primary and metastatic disease for either gene product. Studies that include clinical data are needed to clarify the significance of these findings and to evaluate whether these markers will help predict prognosis in tumors.
 ...
PMID:Immunohistochemical evaluation of E-cadherin and epidermal growth factor receptor in non-small cell lung cancer. 756 48

CD44 cell-surface receptor expresses multiple isoforms, some of which are believed to play a role in tumor growth and metastasis. The CD44 gene is composed of 19 exons, of which 9 (exons 6 to 14) are alternatively spliced to form inclusions in the intervening membrane proximal region. Sequences present in the shortest metastatic variant cloned from a rat metastatic cell line have been shown to correspond to human exons 10 and 11, also called exons v6 and v7. Using RT-PCR, we have addressed in detail the CD44 isoforms produced in human breast and colon tumors. We analyzed 53 breast-tumor- and 58 colon-tumor-related samples as well as 1 benign mastopathy, 1 normal breast, 4 non-invaded lymph nodes and 8 normal colon tissues. All tumors analyzed expressed the hemopoietic CD44 (CD44H) isoform (no alternatively spliced exons added), whereas 81% expressed the CD44E form (addition exons 12, 13 and 14). Furthermore, 85% of tumors presented complex patterns of expression, with an average number of 5 to 6 bands detected. In view of their implication in the metastatic process, we investigated in greater detail the isoforms containing exons 10 and 11 (v6 and v7). Exon 10 was more frequently expressed than exon 11, 80% and 57% of the samples respectively. The great majority of cases showed ladder-like patterns starting from the shortest forms (exons 5-10 or 5-10-11) and larger-molecular-weight bands corresponding predominantly to sequential inclusions of exons from 3' to 5'. Exon-10 and exon-11 variants were also found in one benign mastopathy. The majority of normal tissues (1 breast and 6/8 colon) expressed only the CD44H isoform. These data indicate that expression of metastatic variants is common in human breast and colon tumors and can occur early during cancer progression, as testified by their presence in a benign breast tumor. While expression of exon-10 variants were correlated with presence of distal metastases in colon tumors, exon-11 variants were not (metastatic events were too rare in our breast-tumor series to reach significance). This suggest that exon 10 may correspond to the minimal sequences required to favor metastatic events.
 ...
PMID:CD44 expression patterns in breast and colon tumors: a PCR-based study of splice variants. 759 9

To examine whether renal cell carcinoma displays altered CD44 expression we performed reverse transcription-polymerase chain reaction (RT-PCR) analysis of CD44 in 38 specimens from renal cancer, normal kidney and metastases of 19 patients and 6 renal cancer cell lines. To detect the CD44 variants, we utilized the RT-PCR Southern blot method. One out of 19 (5.3%) renal cancer specimens expressed a larger molecular weight band than 1 kb by RT-PCR analysis, in contrast to previous findings in colon and breast cancer. The band patterns in RT-PCR were different in 14/17 (82.4%) cases between normal kidney and tumors, and a band of about 700 bp was especially marked in 12/17 (70.6%) tumor specimens and 4/6 (66.7%) cell lines. By cloning and sequencing of the 700 bp band, we found that this variant is identical to the CD44 variant sharing only exon v10. Examination by Northern blot analysis has revealed that all tumors express a higher level of CD44 mRNA than paired normal kidneys. These findings suggested that the CD44 variants sharing exon v10 play some role in renal cancer.
 ...
PMID:High-level expression of the CD44 variant sharing exon v10 in renal cancer. 759 62

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.
 ...
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.
 ...
PMID:Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma. 763 25

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

Decreased E-cadherin expression assessed by immunohistochemistry correlates with poor survival of bladder and prostate cancer patients. The clinical usefulness of this parameter should therefore be evaluated in a large-scale prospective study. E-cadherin is an epithelial cell-cell adhesion molecule and impaired function presumably leads to increased invasive capacity of the cells. It has been shown that defective function can result from several mechanisms: mutation of the gene, alteration of transcription, posttranslational modification or changes in the interaction of E-cadherin with cytoskeleton anchoring proteins--the catenins. A major mechanism leading to decreased E-cadherin expression in tumors lies in decreased transcription of the gene. Hence, a better understanding of the regulation of E-cadherin transcription might open avenues for therapy by restoring normal expression.
Invasion Metastasis
PMID:Defective E-cadherin function in urological cancers: clinical implications and molecular mechanisms. 765 35

Specific CD44 variant glycoproteins are overexpressed at particular stages of colorectal tumor progression. Some variants of the CD44 glycoprotein without exon v6 sequences appear at the earliest stage of tumorigenesis, i.e., in early adenomas. Expression of variants containing exon v6 sequences is largely restricted to the advanced stages of tumor development and in addition is more prevalent and intense in metastatic (Dukes C/D) than in nonmetastatic (Dukes A/B) carcinomas. The observation that CD44 variants containing a protein domain of CD44 that confers full metastatic potential to rat carcinoma and sarcoma cell lines is increasingly expressed during colorectal tumor progression indicates that this domain may have an important role in tumor progression and metastasis in humans. Information on v6 expression, which can be obtained by routine immunohistochemistry, may prove of important prognostic value, particularly in carcinomas (Dukes A and B) that have not yet given rise to detectable metastases.
 ...
PMID:Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. 769 4

We have examined the cell surface molecule CD44, which is attracting interest because of reports that isoforms are associated with metastasis. The prognostic value of CD44 expression has yet to be assessed for a solid tumour. Benign (59) and malignant (primary 61, metastatic 59) gastric tissues were examined with antibodies directed at epitopes common to known CD44 isoforms. Normal mucosa was CD44 negative. In atrophic gastritis and intestinal metaplasia expression was restricted to the epithelial cells of the basal glands and was positively correlated with an increased leucocyte infiltrate and with the expression of HLA DR by mucosal cells. These observations suggest a role for chronic inflammation in the induction of CD44 expression on benign mucosa. No such association was observed between inflammatory infiltrate and CD44 expression on gastric tumours. CD44 expression, observed in only 49% of primary tumours, was associated with distant metastases at time of diagnosis and, among 31 curatively resected patients, with tumour recurrence (p = 0.0014) and increased mortality (p = 0.001) during follow-up averaging 17 months. When we used an antibody directed against the CD44 variant exon 9v, we found a good correlation between the expression of total CD44 and of exon 9v containing isoforms, and 9v expression in primary tumours was significantly and positively associated with tumour recurrence and mortality.
 ...
PMID:De-novo expression of CD44 and survival in gastric cancer. 769

Loss of expression of the cell-cell adhesion molecule E-cadherin has been shown to have a potential role in the dedifferentiation and progression of many human malignancies. We applied immunohistochemical staining for E-cadherin to eight formalin-fixed, paraffin-embedded primary and matched metastatic human head and neck carcinomas. In tumors that contained both well-differentiated and poorly differentiated components, staining was notably reduced in the poorly differentiated cells. Staining was nearly identical or only slightly reduced in metastases compared to primary tumors. As found in previous reports, E-cadherin expression may be involved in the dedifferentiation of these tumors.
 ...
PMID:Immunolocalization of E-cadherin in human head and neck cancer. 780 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>