Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor metastasis is one of the most life-threatening aspects of tumor progression in patients with cancer. One of the cell surface molecules that has been implicated to play an important role in tumor metastasis is CD44. Earlier results provide the initial optimism that CD44 isoform expression may be a marker for human cancers. However, more recent studies revealed that regulation of CD44 isoform expression is a complex and not well-understood phenomenon. Expression of CD44 in tumor cells can be regulated quantitatively by increasing the expression of one particular CD44 isoform or quantitatively by altering the expression of CD44 isoforms. Downregulation of CD44 is important in the metastasis of some tumor cells. We summarize some of the recent results on the potential of CD44 as a diagnostic or prognostic marker for patients with cancers.
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PMID:CD44 as a marker in human cancers. 909 May 2

CD44, a family of closely related glycoproteins generated by alternative splicing, as well as the increased beta 1,6-branching of Asn-linked oligosaccharides (beta 1,6-branches), have been implicated in tumor progression and metastasis. We have investigated the expression of CD44 standard (CD44s), various CD44 splice variants (CD44v3, -v4, -v5, -v6 and -v9), and of beta 1,6-branches in a total of 37 paraffin-embedded human primary melanomas and metastases. Out of the 28 studied primary melanomas, 27 were positive for CD44s, 21 for CD44v5 (cytoplasmic staining) and 26 for beta 1,6 branches. Furthermore, superficial spreading melanomas showed a significant (p = 0.004) stronger staining for CD44s than the thick (> 1.5 mm) nodular melanomas, whereas no significant difference was found with regard to staining for CD44v5 and beta 1,6-branches. Eight of the 9 studied melanoma metastases were positive for CD44s, 6 for CD44v5 (cytoplasmic staining) and 7 for beta 1,6-branches. No CD44v3, -v4, -v6 and -v9 could be detected in any of the tumors. On average, metastases as compared to primary tumors, exhibited a significant (p = 0.002) weaker staining for CD44s. However, metastasizing melanomas could not be distinguished from non-metastasizing ones based on CD44 immunostaining.
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PMID:Expression of CD44 isoforms and beta 1,6-branched oligosaccharides in human malignant melanoma is correlated with tumor progression but not with metastatic potential. 913 10

CD44 is the principal cell surface receptor for hyaluronate. Variant forms of the receptor, produced by alternative splicing, have been found to be associated with tumor progression in a variety of cancers. Based on investigations at the RNA level, it has recently been proposed that expression of CD44 variant V2 was present in urothelial cancer but not in normal urothelium. Since a distinctive marker for urothelial cancer would be extremely useful, frozen sections of normal urothelium and urothelial cancer were examined for expression of standard CD44 and CD44V2. Frozen sections of specimens of 35 patients with transitional cell carcinoma of the bladder, 16 specimens of normal bladder and 5 ureters were examined. Immunohistochemical staining was performed using a polyclonal antibody to CD44V2 (PAB CD44V2), a monoclonal antibody to CD44V2 (MAB CD44V2) and a monoclonal antibody to CD44S (MAB CD44S). CD44V2 and CD44S were also measured in lysates of urine sediments from 21 patients by enzyme-linked immunoabsorbent assay (ELISA). All investigated transitional cell carcinomas expressed CD44V2. There was no differentiation between invasive and noninvasive carcinoma. CD44V2 was also expressed in normal urothelium. Standard CD44 was expressed by the transitional cell carcinoma, normal urothelium, musculature and interstitial tissue. The amount of CD44V2 and CD44S in lysates of urine sediments is not correlated to diagnosis. In contrast to investigations at the RNA level, CD44V2 on the protein level seems not to be a distinctive marker for urothelial cancer. Therefore, CD44V2 will not be a useful diagnostic marker for detection of transitional cell carcinoma.
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PMID:Expression of CD44V2 in transitional cell carcinoma of the urinary bladder and in urine. 922 71

A glycoprotein extract (CVS), derived from the unicellular green alga Chlorella vulgaris, strain CK22, exhibited a pronounced antitumor effect against both spontaneous and experimentally induced metastasis in mice. Inhibition of tumor metastasis was enhanced when intratumor administration of CVS was followed by s.c. injection of CVS. Anti-metastatic immunopotentiation was observed in euthymic mice, but not in athymic nude mice. The antitumor activity of CVS was reflected in antigen-specific, T-cell-mediated immunity. Both CD4 and CD8 T cells contributed to the antimetastatic effects, as shown by in vivo depletion experiments with anti-T-cell subset antibodies. Furthermore, CVS caused the recruitment of T cells to the regional lymph nodes and their proliferation in these organs. The CD4-positive population, following CVS injection at the time of tumor rechallenge, displayed a pronounced increase in the proportion of T cells that were CD18 bright, CD44 bright, CD25+, CD54+, CD69+ or CD71+ in the lymph nodes. Thus, CVS induces T cell activation in peripheral lymph nodes in tumor-bearing mice. We conclude that CVS augments antimetastatic immunity through T cell activation in lymphoid organs and enhances recruitment of these cells to the tumor sites. Presurgical treatment with CVS might prevent metastasis or tumor progression.
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PMID:A novel glycoprotein obtained from Chlorella vulgaris strain CK22 shows antimetastatic immunopotentiation. 949 Feb 1

Immunolocalization of E-cadherin (E-cad), alpha-catenin, beta-catenin, and CD44 has rarely been investigated in human cholangiocarcinoma (CC). We, therefore, immunohistochemically examined the expression of E-cad, alpha-catenin, beta-catenin, CD44 standard (CD44s), and CD44 variants (CD44v) including CD44v5, CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and the results were then correlated with tumor grade, vascular invasion, metastasis, p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression. In normal livers, E-cad, alpha-catenin and beta-catenin, but not CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10, were expressed at the cell membrane of normal intrahepatic bile ducts. In CC, membranous expression of E-cad, alpha-catenin, and beta-catenin was the same or reduced when compared with non-cancerous bile ducts in the majority of CC. We found that the down-regulation of E-cad, alpha-catenin, and beta-catenin expression significantly correlated with tumor high grade, but not with vascular invasion, metastasis, p53 expression, Ki-67 labeling, or c-erbB2 expression, except for beta-catenin, the down-regulation of which was associated with c-erbB2 down-regulation. CD44s, CD44v5, CD44v6, CD44v7-8 and CD44v10 were frequently expressed at the membrane of CC cells. There were, however, no significant correlations between these aberrant CD44 expression and tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c-erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s aberrant expression significantly correlated with absence of metastasis and vascular invasion, and that CD44v5 aberrant expression significantly correlated with p53 under-expression. These results suggest that membranous expression of E-cad, alpha-catenin, and beta-catenin is reduced in a majority of CC and this down-regulation correlates with CC high grade, and that beta-catenin down-regulation is associated with c-erbB2 down-regulation. The data also suggested that CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis of CC but this neoexpression does not correlate with tumor progression in CC, with the exception of CD44s and CD44v5.
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PMID:Expression of E-cadherin, alpha-catenin, beta-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: an immunohistochemical study. 953 36

Markers of cell proliferation (MIB-1), differentiation (S-100 protein, cytokeratin, transthyretin, GFAP, EMA, CEA), and cell adhesion (CD44) were analyzed immunohistochemically in a biopsy series of 21 chorioid plexus tumors determine their correlation with histological grade and impact on clinical course. The material included 8 papillomas (WHO grade I) and 8 carcinomas (WHO grade III); another 5 tumors were tentatively classified as atypical papilloma. The MIB-1 labeling index of papillomas was 3.7%, while that of carcinomas was 14%. Atypical papillomas (mean: 6%) failed to segregate as a statistically different group. The age and sex of patients, and tumor localization were found not to influence MIB-1 reactivity. High MIB-1 labeling indexes were associated with less favourable postoperative outcome. S-100 protein immunoreactivity was generally reduced in carcinomas, while most tumors were positive for transthyretin and cytokeratin irrespective of their MIB-1 status. Positivity for GFAP and EMA was detected in some tumors of both low- and high grade. CEA was universally negative. The standard isoform of CD44 was only expressed in atypical papillomas and 4 carcinomas showing focal infiltration of adjacent tissues. Western-blot analysis was also carried out in 5 cases to detect CD44. Quantitation of MIB-1 immunohistochemistry may, thus, prove a more readily accessible ancillary method for assessing chorioid plexus neoplasms than analysis of differentiation markers. Our data also suggest that expression of CD44H is instrumental in conferring invasive potential to these tumors and possibly contributes to tumor progression as well.
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PMID:[Prognostic markers in the histopathological diagnosis of tumors of the choroid plexus]. 957 5

In order to clarify the relation between expression of individual CD44 variant exons and tumor progression, 34 endometrial carcinomas (endometrioid type) were investigated, as well as 27 samples of normal endometrium, using a combination of reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization (SBH). Western blotting was also performed for comparison of protein levels with the results of the RT-PCR/SBH methods. Analysis of gross CD44 splicing patterns demonstrated high-level expression of variant isoforms in endometrial carcinomas as compared with normal endometrium. Exon-specific RT-PCR/SBH assays revealed large, abundant transcripts of individual variant exons in particular v3, v4, and v5, in tumors, but these isoforms were also expressed in normal endometria, suggesting a lack of tumor-specificity. No individual CD44 variant transcripts were associated with any of the prognostic factors investigated. Parallel observations showed variant CD44 transcripts to be more readily detectable than protein isoforms in the same samples. These findings indicate that in endometrial carcinomas, expression of individual variant CD44 exons is markedly up-regulated, but this molecule may not be useful as a consistent indicator of tumor progression.
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PMID:Up-regulation of CD44 variant exon expression in endometrial carcinomas: analysis of mRNA and protein isoforms, and relation to clinicopathological factors. 960 Jan 23

Expression of cell surface molecules that mediate cell-matrix and cell-cell interactions largely contributes to the ability of melanoma cells to migrate and spread beyond the primary site of the tumor. CD44, the principal cell-surface receptor for hyaluronate, and its numerous splice variants have been reported to play a crucial role in invasion and the metastatic process of different human neoplasms, including primary malignant melanoma (PMM). The aim of this study was to clarify which isoforms of CD44 (standard CD44 and CD44 variants) are distributed in PMM with a vertical tumor thickness of >1.4 mm. Staining of CD44 standard (CD44s) and splice variants was further examined for diagnostic and prognostic relevance in a panel of melanocytic skin lesions. Ten cases of PMM with Breslow >1.4 mm were analysed by immunohistochemistry using monoclonal antibodies specific for CD44s and the splice variants v3, v5, v6, v7, v7-8, and v10. In addition, using anti-CD44s, v5, and v6 antibodies, 55 melanocytic lesions, including dermal nevi (n=12), Clark nevi (dysplastic nevi) (CN; n=11), melanoma in situ (Mis; n=8), PMM (n=18), and cutaneous metastasis of malignant melanoma (cMMM; n=6) were assessed. Staining intensities were scored visually and evaluated by means of a staining index. In ten cases of PMM with a Breslow index >1.4 mm positive staining was ascertained for CD44s, v5 and for v6 in three cases. No staining was found for v3, v7, v7-8, and v10. Examination of CD44s, v5, and v6 in 55 melanocytic skin lesions revealed a high index for CD44s in all specimens and a weak staining of v5 in Mis; dermal nevi and CN did not stain for v5. However, in PMM and cMMM we found v5 to be strongly positive. The isoform v6 showed a variable index only in PMM, but without connection to established prognostic criteria. We conclude that CD44s and splice variants can not be regarded as indicators for tumor progression in malignant melanomas. However, v5 may potentially serve as a diagnostic marker for melanocytic skin lesions.
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PMID:CD44 and variants in melanocytic skin neoplasms. 960 38

CD44, a major hyaluronan receptor, exists as several isoforms and is widely distributed in different cells and tissues. The isoforms of CD44, such as CD44s (the standard form), CD44E (the epithelial form) and CD44v (variant isoforms) (arise from differential splicing of one to ten (or eleven) variable exons that encode portions of the membrane proximal extracellular domain. The molecular diversity of CD44 isoforms is further compounded by differential biosynthetic processes and post-translational modifications [e.g. N-/O-glycosylation or glycosaminoglycan (GAG) addition]. This structural arrangement, which occurs within either the invariant region or the extracellular domain of the variant region, is important for CD44-mediated communication between extracellular matrix materials [ECM-hyaluronic acid (HA), collagen and fibronectin] and intracellular protein components (e.g cytoskeletal proteins and various regulatory enzymes). The 15 amino acid sequence [e.g. NSGNGAVEDRKPSGL (in human) or NGGNGTVEDRKPSEL (in mouse)] residing in the cytoplasmic domain of CD44 isoforms is the ankyrin-binding domain of this family of transmembrane glycoproteins. Biochemical analyses plus in vitro mutagenesis indicate that the ankyrin-binding domain is required for CD44-mediated "outside-in" and "inside-out" cell activation events. Furthermore, CD44s-cytoskeleton interaction is tightly coupled with signal transducing molecules (e.g. p185HER2 or Src kinases) during oncogenic signaling. Moreover, the transmembrane linkage between CD44v isoforms (CD44v10 and CD44v3) and the cytoskeleton up-regulates invasive and metastatic-specific tumor phenotypes [e.g. matrix degradation (MMPs) activities, tumor cell invasion and migration]. These findings strongly suggest that the interaction between CD44 isoforms and the cytoskeleton plays a pivotal role in the onset of oncogenesis and tumor progression.
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PMID:CD44 isoform-cytoskeleton interaction in oncogenic signaling and tumor progression. 963 39

An intensive search continues for reliable markers that would be clinically useful in the diagnosis of small tumors and in the evaluation of their predicted clinical outcome. One potential marker, extensively studied in human samples is the cell surface adhesion molecule CD44. The single CD44 gene codes for a large family of cell surface proteins by alternative splicing and severe abnormalities have been observed in the patterns of its expression in many types of human tumors using both protein and RNA-based analyses. These abnormalities are manifested by markedly increased levels of unusual transcripts and proteins in tumor cells compared to the corresponding normal tissues. Aberrant processing of immature CD44 transcripts has also been observed in tumor cells and this can lead to the inappropriate retention of introns and to the use of cryptic splice sites in the mRNA. Inappropriate expression patterns of the alternatively spliced exons have also been linked both to tumor progression and to metastatic potential. The clinical relevance of all these observations is demonstrated by the frequent detection of these abnormalities in samples from malignant tumors of many different organs and by their presence in pre-invasive and high risk pre-cancerous lesions. This article reviews the current information regarding the expression of the CD44 gene in tumor cells and its potential use as a marker in clinical evaluation. The overall conclusion is that with the use of the latest assay techniques and perhaps in combination with other molecular markers, analysis of CD44 expression can provide new and powerful assays for the detection of neoplastic disease.
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PMID:Clinical implications of anomalous CD44 gene expression in neoplasia. 963 41


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