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)

There is a great need for markers that distinguish slowly progressive from rapidly progressive prostate cancers in paraffin-embedded tissues. CD44, an adhesion molecule that has been useful for the prediction of prognosis in some other cancers, has not been described in prostate cancer. The expression of CD44 was investigated with the monoclonal antibody GKW.A3 in prostate cancer in formalin-fixed, paraffin-embedded tissue sections of (1) whole prostates from 50 patients with 74 prostate cancers; and (2) lymph node metastases from 14 patients. Sixty percent of primary prostate cancers expressed CD44 moderately to strongly. No metastases expressed CD44 moderately to strongly; only 14% of metastases expressed even low levels of immunohistochemically detectable CD44. There is a difference between primary and metastatic prostate cancer (P <.0006) in the expression of CD44 and an inverse correlation (P <.05) between histological differentiation (Gleason grade) and the expression of CD44. The magnitude of the differential expression of CD44 in primary and metastatic prostate cancers suggests it should be investigated as an indicator of prognosis in a large prospective study.
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PMID:Altered expression of CD44 in human prostate cancer during progression. 892 76

Cell adhesion molecules mediate cell-cell and cell-matrix interactions, and they are thought to play an important role in tumor invasion and metastasis. Altered expression of integrins and CD44 in renal cell carcinoma has been recently demonstrated, but an association with invasive or metastatic behavior has not been reported. We examined very late activation (VLA) integrin and CD44 expression in 37 renal cell carcinomas and correlated adhesion molecule expression with multiple histological and clinical parameters. Most tumors exhibited positive staining for VLA3 (81%). Approximately one third of the tumors stained positively for VLA6 and CD44, and fewer (27%) were positive for VLA2. Only a few tumors were positive for VLA4 (8%) and VLA5 (14%). Most of the tumors exhibiting positive staining showed a combination of membranous and cytoplasmic staining patterns. Low-grade tumors positive for VLA6 showed a tendency for basilar staining of the tumor cells, whereas high-grade tumors exhibited diffuse cytoplasmic staining. All tumors exhibiting weak or strong positive staining for VLA4 or VLA5 showed extrarenal invasion or were known to have developed metastases at the time of nephrectomy. All tumors strongly positive for VLA2 or CD44 showed invasion beyond the renal capsule or metastases. In contrast to a previous study, no association was observed between positive staining and tumor grade. Nor were tumor size, architectural pattern, cell type, or DNA ploidy found to be associated with particular staining patterns. Although many of the invasive tumors showed no difference in VLA integrin or CD44 expression compared with tumors confined to the kidney, increased expression in some of them suggests that these cell adhesion molecules may contribute to the invasive or metastatic phenotype.
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PMID:Correlation of very late activation integrin and CD44 expression with extrarenal invasion and metastasis of renal cell carcinomas. 895 11

This study compared phenotype and behaviour of seven head and neck squamous cell carcinoma (HNSCC) cell lines and normal epithelial cells. Indications were found that in HNSCC cells: 1) loss of the cell-cell adhesion molecule E-cadherin was correlated with loss of epithelioid cell morphology but not with loss of cell-cell cohesion; 2) reduced expression of the cell-cell adhesion molecule desmoglein was unrelated to cell shape or motility; 3) high expression of the cell-substrate adhesion molecule alpha 6 beta 4, a receptor for laminin, corresponded with epithelioid colony formation while, in our adhesion assay, low expression of alpha 6 beta 4 paradoxically coincided with an increased adhesion to laminin; 4) presence of vimentin intermediate filaments coincided with loss of anchorage dependency. We propose that by simultaneous downregulation of E-cadherin, replacement of alpha 6 beta 4 by an aberrant laminin receptor and co-expression of vimentin a malignant phenotype arises of spindle-shaped, motile, anchorage-independent HNSCC cells with enhanced laminin-binding capacity.
Clin Exp Metastasis 1996 Nov
PMID:Adhesion properties, intermediate filaments and malignant behaviour of head and neck squamous cell carcinoma cells in vitro. 897 May 80

Graft-versus-leukemia (GVL) and Graft-versus-host (GVH) reactions were compared after systemic transfer of allogeneic antitumor immune T lymphocytes from B10.D2 (H-2d; Mls(b)) into DBA/2 (H-2d; Mis(a)) mice. Before immune cell transfer, recipient DBA/2 mice were sublethally irradiated with 5 Gy to prevent host-versus-graft reactivity. Recipients were either bearing syngeneic metastatic ESb lymphomas (GVL system) or were normal, non-tumor-bearing mice (GVH system). We previously reported that this adoptive immunotherapy protocol (ADI) had pronounced GVL activity and led to immune rejection of even advanced metastasized cancer. In this study, monoclonal antibodies were used for immunohistochemical analysis of native frozen tissue sections from either spleen or liver to distinguish donor from host cells, to differentiate between CD4 and CD8 T lymphocytes, and to stain sialoadhesin-positive macrophages at different time points after cell transfer. The kinetics of donor cell infiltration in spleen and liver differed in that the lymphoid organ was infiltrated earlier (days 1 to 5 after transfer) than the nonlymphoid organ (days 5 to 20). After reaching a peak, donor cell infiltration decreased gradually and was not detectable in the spleen after day 20 and in the liver after day 30. The organ-infiltrating donor immune cells were mostly T lymphocytes and stained positive for CD4 or CD8 T-cell markers. A remarkable GVL-associated observation was made with regard to a subset of macrophages bearing the adhesion molecule sialoadhesin (SER+ macrophages). In the livers of tumor-bearing mice, their numbers increased between days 1 and 12 after ADI by a factor greater than 30. Double-staining for donor cell marker and SER showed that the sialoadhesin-expressing macrophages were of host origin. The SER+ host macrophages from GVL livers were isolated by enzyme perfusion and rosetting 12 days after ADI, when they reached peak values of about 60 cells per liver lobule, and were tested, without further antigen addition, for their capacity to stimulate an antitumor CD8 T-cell response. The results of this immunologic analysis suggest that these cells in the liver function as scavengers of the destroyed metastases and as antigen-processing and -presenting cells for antitumor immune T cells.
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PMID:Differences between graft-versus-leukemia and graft-versus-host reactivity. I. Interaction of donor immune T cells with tumor and/or host cells. 905 44

CD44 is a ubiquitous multistructural and multifunctional cells surface adhesion molecule involved in cell-cell and cell-matrix interactions. Twenty exons are involved in the genomic organization of this molecule. The first five and the last 5 exons are constant, whereas the 10 exons located between these regions are subjected to alternative splicing, resulting in the generation of a variable region. Differential utilization of the 10 variable region exons, as well as variations in N-glycosylation, O-glycosylation, and glycosaminoglycanation (by heparan sulfate or chondroitin sulfate), generate multiple isoforms (at least 20 are known) of different molecular sizes (85-230 kDa). The smallest CD44 molecule (85-95 kDa), which lacks the entire variable region, is standard CD44 (CD44s). As it is expressed mainly on cells of lymphohematopoietic origin, CD44s is also known as hematopoietic CD44 (CD44H). CD44s is a single-chain molecule composed of a distal extracellular domain (containing, the ligand-binding sites), a membrane-proximal region, a transmembrane-spanning domain, and a cytoplasmic tail. The molecular sequence (with the exception of the membrane-proximal region) displays high interspecies homology. After immunological activation, T lymphocytes and other leukocytes transiently upregulate CD44 isoforms expressing variant exons (designated CD44v). A CD44 isform containing the last 3 exon products of the variable region (CD44V8-10, also known as epithelial CD44 or CD44E), is preferentially expressed on epithelial cells. The longest CD44 isoform expressing in tandem eight exons of the variable region (CD44V3-10) was detected in keratinocytes. Hyaluronic acid (HA), an important component of the extracellular matrix (ECM), is the principal, but by no means the only, ligand of CD44. Other CD44 ligands include the ECM components collagen, fibronectin, laminin, and chondroitin sulfate. Mucosal addressin, serglycin, osteopontin, and the class II invariant chain (Ii) are additional, ECM-unrelated, ligands of the molecule. In many, but not in all cases, CD44 does not bind HA unless it is stimulated by phorbol esters, activated by agonistic anti-CD44 antibody, or deglycosylated (e.g., by tunicamycin). CD44 is a multifunctional receptor involved in cell-cell and cell-ECM interactions, cell traffic, lymph node homing, presentation of chemokines and growth factors to traveling cells, and transmission of growth signals. CD44 also participates in the uptake and intracellular degradation of HA, as well as in transmission of signals mediating hematopoiesis and apoptosis. Many cancer cell types as well as their metastases express high levels of CD44. Whereas some tumors, such as gliomas, exclusively express standard CD44, other neoplasms, including gastrointestinal cancer, bladder cancer, uterine cervical cancer, breast cancer and non-Hodgkin's lymphomas, also express CD44 variants. Hence CD44, particularly its variants, may be used as diagnostic or prognostic markers of at least some human malignant diseases. Furthermore, it has been shown in animal models that injection of reagents interfering with CD44-ligand interaction (e.g., CD44s- or CD44v-specific antibodies) inhibit local tumor growth and metastatic spread. These findings suggest that CD44 may confer a growth advantage on some neoplastic cells and, therefore, could be used as a target for cancer therapy. It is hoped that identification of CD44 variants expressed on cancer but not on normal cells will lead to the development of anti-CD44 reagents restricted to the neoplastic growth.
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PMID:CD44: structure, function, and association with the malignant process. 911 68

The expression of specific cell-adhesion molecule CD44 isoforms (splice variants) is associated with metastatic spread and poor prognosis in human malignancies. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in early-stage cervical cancer. We used 4 different variant exon sequence-specific murine monoclonal antibodies to the CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 to study the prognostic value of CD44 splice variants in 200 cases of International Federation of Gynecology and Obstetrics (FIGO) stage-IB cervical cancer by immunohistochemistry. In the univariate analysis, the expression of CD44v3 (log-rank test, p = 0.03) and CD44v6 (log-rank test, p = 0.03) was correlated with poor overall survival. In the subgroup of patients without metastatic disease in the pelvic lymph nodes, expression of CD44v6 was correlated with poor disease-free and overall survival (log-rank test, p = 0.04 and p = 0.01, respectively). Multivariate analysis, correcting for the confounding variables pelvic lymph-node involvement, depth of invasion and histologic grading, revealed CD44v6 to be an independent prognostic factor for overall survival of patients with early-stage cervical cancer. The results of this study indicate that CD44v6 is an additional prognostic marker in surgically treated cervical cancer. The assessment of CD44 isoform expression could be of clinical value in deciding upon adjuvant therapy, resulting in a more individualized management of therapy.
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PMID:CD44 is an independent prognostic factor in early-stage cervical cancer. 913 53

The National Breast Screening Programme affords the opportunity to study breast carcinomas at an early stage in their development. E-cadherin is a calcium-dependent, intercellular adhesion molecule whose loss of expression may facilitate the processes of invasion and metastasis of some human tumours. From a group of screen-detected ductal carcinomas less than or equal to 10 mm in diameter, 16 with lymph node metastasis were identified and matched for grade, size and patient age with node negative tumours. The level of expression of E-cadherin (detected by immunocytochemistry) was compared in the matched pairs using a simple semi-quantitative intensity distribution scoring system. The results showed a significant (P = 0.05 Wilcoxon paired rank test) reduction of E-cadherin expression in tumours with lymph node metastases compared to those without. In the context of the small size of these tumours it is proposed that these results support the hypothesis that reduction in E-cadherin expression is an early event in the development of metastases.
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PMID:Loss of E-cadherin expression associated with lymph node metastases in small breast carcinomas. 913 39

IL-10 is a cytokine which shows various effects including inhibition of T-cell proliferation or HLA-dependent antigen presentation. In this study, we analysed the effects of exogenous or autocrine IL-10 on proliferation and expression of immunocritical surface molecules. Fourteen cultures of human melanoma cells were established from primary melanomas, locoregional lymph-node or distant metastases. In 5 melanoma cell cultures, proliferation in the presence of IL-10, anti-IL-10 antibodies (Ab) or control Ab was assessed with colorimetric and [3H]thymidine uptake assays. Flow cytometric analysis was used to quantify the expression of human leukocyte antigen (HLA) class-I, HLA class-II and intercellular adhesion molecule (ICAM)-1 and the IL-10 receptor (IL-10R). IL-10 production of melanoma cells was documented by RT-PCR and IL-10 protein was detected in the supernatants by means of ELISA. IL-10 enhanced proliferation and prolonged survival of melanoma cells in 5 out of 5 cultures. Anti-IL-10 Ab decreased proliferation. IL-10R expression was found in 12 out of 14 (86%) melanoma cell cultures. The expression of HLA-I, HLA-II and ICAM-1 on all melanoma cells that were positive for IL-10R showed a reduction of 10-60% by IL-10, whereas the surface levels of HLA-I, HLA-II and ICAM-1 in 5 out of 5 cell cultures revealed an increase of 10-170% by anti-IL-10 Ab. These findings suggest that IL-10 is an autocrine growth factor with significant impact on immunocritical molecules in melanoma. IL-10 effects have to be considered when planning therapeutic immunointerventions in melanoma patients.
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PMID:Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules. 917 19

A retrospective immunohistochemical analysis of the adhesion molecule E-cadherin (E-CD) was performed in 112 differentiated thyroid carcinomas and 38 synchronous and 20 relapse metastases primarily from operations performed at the Medical School Hanover between 1982 and 1992. E-CD-specific antibody 5H9 was applied to paraffin-embedded tissues. All patients were clinically followed for a maximal period of 12 years. Lack of E-CD expression i.e., <5% of tumor cells positive) occurred in 18 of 112 (16.1%) cases, whereas the majority showed either low (24.1%), medium (35.7%), or high (24.1%) positivity. No difference was found between papillary (n = 88) and follicular (n = 24) carcinomas. Univariate statistical analysis for survival (Kaplan-Meier) showed that lack of E-CD expression (P < 0.024) is an adverse prognostic factor for differentiated thyroid carcinomas. The highest significance was seen among patients without lymph node involvement at first presentation (pN(0); P = 0.0068) and among females (P = 0.0033). Multivariate analysis (Cox model) indicated that E-CD staining is an independent prognostic factor (corrected risk factor, 3.7; P < 0.03) in addition to distant metastasis (pM1) and tumor size. A comparison of E-CD stainings between primary tumors and their metastatic lesions showed similar results in both synchronous and relapse metastases after therapy. In conclusion, E-CD immunostaining is an independent prognostic indicator for differentiated thyroid carcinomas. It may help to uncover the small group of patients with differentiated thyroid carcinomas carrying a high risk of suffering an unfavorable clinical outcome.
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PMID:Immunohistochemical detection of E-cadherin in differentiated thyroid carcinomas correlates with clinical outcome. 919 32

Primary infiltrating ductal carcinomas (IDCs) of the breast which measure less than 0.5 cm (T1a lesions) and between 0.5 and 1.0 cm (T1b lesions) are associated with a small risk of nodal metastasis. The role of axillary dissection in T1a and T1b breast cancer is controversial. In the absence of axillary dissection, comparable prognostic information might be obtained by examination of the primary cancer. The adhesion molecule CD44 represents a family of transmembrane proteins that mediate cell-cell and cell-matrix interactions. Previous investigators have correlated expression of CD44 and its isoforms with prognosis in breast cancer. We investigated the value of CD44 isoform expression as a predictor of nodal metastases in nonpalpable T1a and T1b IDC. Monoclonal antibody against the standard form of CD44 (CD44s) and polyclonal antibody directed against the variant isoform (CD44v6) was tested on 34 cases of nonpalpable node-negative infiltrating ductal carcinoma (IDC) less than 1.0 cm and 9 cases of nonpalpable node-positive IDC less than 1.0 cm. The expression of CD44s was significantly decreased in node-positive T1a and T1b IDC versus node-negative T1a and T1b IDC (11% vs 65%). In contrast, 97% of the node-negative IDC and 100% of the node-positive IDC expressed the CD44v6 isoform. We conclude that CD44s expression is significantly altered in T1a and T1b IDC with nodal metastases but that the CD44v6 isoform does not correlate with nodal metastases in nonpalpable stage T1a and T1b IDC.
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PMID:Role of CD44 in nonpalpable T1a and T1b breast cancer. 922 43


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