Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A critical step in the metastatic spread of tumour cells is the interaction of circulating tumour cells with the vascular endothelium. We have investigated the role of CD44 and its variants in the adhesion of a human melanoma cell line (RPMI-7951) and a breast adenocarcinoma cell line (MDA-MB-231) to quiescent human umbilical vein endothelial cells (HUVEC) in vitro. Both tumour cell lines express CD44H, CD44A and CD44v9, while HUVEC express only CD44H. Pre-treatment of endothelial cell monolayers with a blocking monoclonal antibody against CD44H (MAb 5A4) reduced the adhesion of RPMI-7951 cells but not that of MDA-MB-231. In contrast, pre-treatment of both tumour cell lines with the same antibody had no effect on adhesion. Digestion of the CD44 ligand hyaluronic acid (HA) on RPMI-7951 cells significantly reduced adhesion to endothelial monolayers, while digestion of HUVEC HA had no effect. We conclude that CD44H expressed on the surface of quiescent endothelial monolayers mediates in part the adhesion of the metastatic melanoma cell line RPMI-7951 but not that of a breast adenocarcinoma line. It does so by acting as a receptor for HA on the tumour cell surface. Tumour cell CD44H and variants CD44A and CD44v9 do not appear to be involved in adhesion to endothelial cells.
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PMID:Endothelial CD44H mediates adhesion of a melanoma cell line to quiescent human endothelial cells in vitro. 862 Dec 36

The scenario of multistep of stomach carcinogenesis differs depending on the two histological types, well differentiated adenocarcinoma and poorly differentiated adenocarcinoma, because the two types may have different genetic pathways. Genetic instability, reactivation of telomerase and abnormal transcript of CD44 including intron 9 are common events of both well and poorly differentiated type carcinomas. These occur at early stage of carcinogenesis, even in precancerous lesions such as intestinal metaplasia and adenoma. Inactivation of APC, activation of K-ras, amplification of c-erbB2, and allelic loss of DCC locus are associated with well differentiated type, while amplification of K-sam and functional loss of cadherin/catenin are characteristics of poorly differentiated type. HGF/c-met system plays a pivotal role in morphogenesis of both histological types through interaction with cell-cell adhesion molecules. Reactivation of telomerase or genetic instability may be an initial event for accumulation of multiple genetic alterations during the progression of stomach carcinogenesis.
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PMID:[Genetic alterations in stomach cancer]. 869 39

A bispecific F(ab')2 antibody conjugate (BAC) was constructed against the complement receptor CR3 of macrophages and variant CD44 (CD44v6) antigen of rat pancreatic adenocarcinoma cells to redirect macrophage-mediated tumor cytotoxicity. The Fab' fragments of monoclonal antibodies (mAb) 1.1ASML and OX42, recognizing the CD44v6 and the CR3 antigens respectively, were chemically coupled at the hinge region using 5,5'-dithiobis(2-nitrobenzoate). The BAC was characterized in vitro for its specific, dual binding capacity to CD44v6 and CR3 antigens. Although the monovalence of the BAC resulted in lower avidities to both the antigens as expected, it was still able to form stable cross-linkages between tumor cells and macrophages in culture leading to the formation of "clump-like" cell aggregates. The in vitro and in vivo tumor-targeting capacity of the BAC was compared with that of the parental antitumor mAb 1.1ASML, which mediates tumor killing by antibody-dependent cell cytotoxicity. These results showed that, even though the bivalent mAb 1.1ASML did not mediate stable cross-linking of target and effector cells, its Fc-receptor-mediated killing of tumor cells was more effective when compared to the BAC. Thus, this study strongly supports the hypothesis that firm persistent binding between effector and target cells per se is not as important as the choice of trigger molecule used for macrophage activation to redirect their tumor cytotoxic potential effectively.
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PMID:Development of a bispecific F(ab')2 conjugate against the complement receptor CR3 of macrophages and a variant CD44 antigen of rat pancreatic adenocarcinoma for redirecting macrophage-mediated tumor cytotoxicity. 883 Jul 37

Different splice variants of the CD44 cell-surface molecule have been linked to metastasis formation in several animal and human cancers. We have used metastatic CSML-100 and non-metastatic CSML-0 mouse adenocarcinoma cell lines to determine whether variant CD44 molecules could be implicated in the different behaviour of these cells. Two CD44 splice variants containing exons v7-v10 and v8-v10 were detected in the non-metastatic CSML-0. Two other mouse cell lines, the normal mammary gland NMuMG and the mammary pre-neoplastic CL-S1 were also found to express these exons. A short (hematopoietic) CD44 isoform was expressed in the metastatic CSML-100 and three other mouse mammary tumour cell lines. Overexpression of v7-v10 and v8-v10 CD44 variants in CSML 100 cells did not decrease their metastatic potential.
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PMID:Expression of CD44 splice variants in metastatic and non-metastatic mouse tumour cell lines. 890

Alternative splicing gives rise to numerous CD44 isoforms, some of which seem to have a role in tumour metastasis. Specifically, a variant form of CD44 with sequences encoded by exon v6 (CD44v6) confers metastatic potential when transfected into a nonmetastasizing cell line of rat pancreatic adenocarcinoma. This study has investigated standard CD44 (CD44s) and CD44v6 expression immunohistochemically in 6 samples of normal pancreatic tissue, 4 of tissue affected by chronic pancreatitis, and 24 of tissue from metastasizing and nonmetastasizing pancreatic adenocarcinomas. In addition, 18 samples from lymph node or visceral metastases were included in the study. CD44s was expressed in nonneoplastic tissue and in tissue from pancreatic adenocarcinomas. In contrast, CD44v6 was not detected in any of the normal tissue or chronic pancreatitis specimens, whereas 54% of pancreatic adenocarcinomas and 55% of metastases expressed this variant exon. Although it is not clear whether CD44 isoforms containing exon v6 play a part in malignant progression in the human exocrine pancreas, it seems plausible that the expression of multiple isoforms containing this and other variant exon confers a selective advantage on pancreatic adenocarcinoma.
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PMID:Differential expression of CD44v6 in adenocarcinoma of the pancreas: an immunohistochemical study. 897 53

CD44 is a cell-surface glycoprotein postulated to play a role in tumor-cell metastasis. We have examined the expression of the standard CD44 (CD44s), and alternative spliced variants of CD44 containing variant exons v6, v9, and v1O (CD44v6, CD44v9, and CD44v10 respectively) in 9 samples of normal cervix, 6 samples of cervical intraepithelial neoplasia (CIN), and 11 samples with invasive cervical carcinomas. RT/PCR demonstrated the presence of CD44s in all samples of normal cervix and those with invasive carcinomas. CD44v6 was also found in all normal cervical samples and in 9 tissue samples of invasive carcinomas. The results also suggested that some tumor specimens had several higher molecular transcripts containing exon v6 compared to specimens of normal cervix. Immunohistochemistry detected the presence of CD44s and the absence of CD44v10 in both epithelial and stromal cells in all specimens. In contrast, CD44v6 and CD44v9 were stained positive in epithelial cells but were absent in stromal cells. The intensity of CD44v6 and CD44v9 staining was strongest in normal cervical epithelium followed by CIN, invasive squamous cell carcinoma, and adenocarcinoma. In the malignant samples, heterogeneity in staining intensity among different clusters of tumor cells was observed. Furthermore, poorly differentiated and undifferentiated carcinomas from patients having poor prognosis did not stain at all. This study suggests that variant CD44 molecules may serve an important function in the cell contact of cervical epithelial cells, and that cervical epithelium acquires heterogeneity in the expression of CD44 adhesion molecules during carcinogenesis, which may be related to tumor metastasis.
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PMID:The expression patterns of standard and variant CD44 molecules in normal uterine cervix and cervical cancer. 899 43

The expression of alternatively spliced CD44 isoforms, especially so-called variant exons v5 and v6, has been shown to correlate with the progression of a number of human cancers examined the expression of standard CD44 and CD44 variants with exons v5 and v6 in 28 cases of human pancreatic tumors (16 cases of invasive duct cell adenocarcinoma and 12 cases of intraductal neoplasms) by immunohistochemistry using exon specific monoclonal antibodies. The expression of standard CD44 was frequently observed in both invasive duct cell carcinomas and intraductal neoplasms. The expression of CD44 variants (v5 and v6) was also seen in almost all duct cell carcinomas. In contrast, intraductal neoplasms infrequently expressed CD44-v5 and -v6, particularly v6 exon. Expression of CD44-v5 and v6 was a common characteristic of invasive cancer, while it was not so prominent in intraductal neoplasm. These findings may be related to the invasiveness of duct cell carcinoma and/or the benign biological behavior of intraductal neoplasm of the pancreas.
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PMID:Expression of CD44 in duct cell carcinomas and in intraductal neoplasms of the pancreas. 906 54

The CD44 transmembrane glycoprotein is expressed in most adult tissues and in the majority of neoplasias. Due to alternative splicing, this cell adhesion molecule exists in multiple isoforms some of which have been associated with specific types of tumours as well as with increased tumour metastasis. In this study, we have looked at the level and type of CD44 expression in lung cancer which represents a histologically heterogenous form of cancer composed of small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), the latter subgroup comprising adenocarcinoma (ADC), bronchio-alveolar carcinoma (BAC), large cell carcinoma (LCC), and squamous cell carcinoma (SCC). We analysed 20 lung cancer cell lines and 64 primary tumours by RT-PCR and immunohistochemical detection of the CD44 standard and variant protein isoforms. Our results suggest that (i) CD44 is expressed in all histologically distinct subsets of lung cancer with a tendency SCC > BAC > ADC > LCC > SCLC, (ii) expression of the CD44 isoforms v5, v7, v8, and, most notably that of CD44 exon v6, strongly correlates with tumours of squamous cell and bronchio-alveolar carcinoma origin, tumours which commonly exhibit a comparatively low metastasizing potential, and (iii) the expression of CD44 isoforms is independent from the tumour size and lymph node status at surgery, the proliferative status of the tumour cell population (Ki67 antigen expression) and the histopathological grading (G1 to G3). Only non-differentiated tumours (G4), which were restricted to SCLC and LCC samples revealed markedly reduced CD44 standard and isoform antigen. In conclusion, our data point to a clear histiotype-related pattern of CD44 variant expression preferentially that of CD44v6 in SCC and BAC.
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PMID:Preferential histiotypic expression of CD44-isoforms in human lung cancer. 915 47

CD44 is a family of transmembrane glycoproteins that act mainly as a receptor for hyaluronan. It can also bind some other extracellular matrix ligands (chondroitin sulphate, heparan sulphate, fibronectin, serglycin, osteopontin) with lower affinity. CD44 is encoded by a single gene containing 20 exons, 10 of which (v1-v10) are variant exons inserted by alternative splicing. The standard, ubiquitously expressed isoform of CD44, does not contain sequences encoded by these variant exons. Numerous variant isoforms of CD44 containing different combinations of exons v1-v10 inserted into the extracellular domain can be expressed in proliferating epithelial cells and activated lymphocytes. CD44 plays a significant role in lymphocyte homing. Both alternative splicing and glycosylation influence receptor function of the molecule, usually reducing its affinity to hyaluronan. The cytoplasmic domain of CD44 communicates with the cytoskeleton via ankyrin and proteins belonging to the ezrin-moesin-radixin family. Relatively little is known about the intracellular events following interactions of CD44 with its ligands. Some variant isoforms, especially those containing sequences encoded by v6-v10, are overexpressed in both human and animal neoplasms. In a rat pancreatic adenocarcinoma model one of the variant CD44 isoforms was proved to be determinant in the metastatic process. For some human neoplasms (carcinomas of the digestive tract, non-Hodgkin's lymphomas, thyroid carcinomas, and others) correlations have been made between the particular pattern of CD44 variants produced by neoplastic cells and clinicopathological parameters of tumours, such as grade, stage, presence of metastases, and survival. In vitro studies indicate that modifications of CD44 expression result in different ligand recognition and influence cell motility, invasive properties, and metastatic potential of experimental tumours. Investigation of CD44 neoexpression can be useful both in early cancer diagnosis and in predicting tumour behaviour. It can also contribute to better understanding of molecular mechanisms leading to neoplastic transformation.
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PMID:CD44 and the adhesion of neoplastic cells. 923 Nov 52

Serum CD44 standard and CD44 variant 6 levels were measured in 45 non-small cell lung cancer (NSCLC) patients and 33 patients with benign lung disease by enzyme-linked immunosorbent assay (ELISA). Expression of CD44 variant 6 in trans-bronchial biopsy specimens from the NSCLC patients was studied by an immunoperoxidase method. CD44 standard and CD44 variant 6 levels in NSCLC patients were not significantly different from those in benign lung disease patients. However, serum CD44 variant 6 level in squamous cell carcinoma patients (226.8 +/- 152.7 ng/ml) was significantly higher than in patients with benign lung disease (154.8 +/- 46.4 ng/ml) (P = 0.011). Neither the serum level of CD44 standard nor that of CD44 variant 6 was correlated with disease Stage and metastasis. CD44 variant 6 expression was most frequently observed in squamous cell carcinoma (P = 0.00058); 15 (79%) of 19 squamous cell carcinoma cases were positive, as were five (22%) of 23 adenocarcinoma cases and two (67%) of three large cell carcinoma cases. Serum CD44 variant 6 levels were 217.1 +/- 143.1 and 156.1 +/- 48.8 ng/ml in patients with and without positive expression of CD44 variant 6, respectively (P = 0.020). Serum CD44 standard and CD44 variant 6 levels are not useful indicators of tumor burden and metastasis in patients with NSCLC. CD44 variant 6 expression might be associated with histological features of NSCLC.
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PMID:Serum CD44 levels in patients with non-small cell lung cancer and their relationship with clinicopathological features. 931 6


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