Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soluble CD44 is present in the serum of normal individuals (2.7 +/- 1.1 nM). The concentration of soluble CD44 in the serum is elevated in patients with advanced gastric (24.2 +/- 9.8 nM) or colon cancer (30.8 +/- 11 nM). Serum CD44 concentration correlated with tumor metastasis and tumor burden. Surgical resection of tumors resulted in decreases in serum CD44 levels. By Western blot analysis, monoclonal anti-CD44 antibody reacted with a major protein with molecular weight between 130,000 and 190,000. In addition, two proteins with molecular weights of 72,000 and 80,000 can also be identified. Therefore, different CD44 isoforms may be present in the serum of cancer patients. Serum CD44 concentrations may be an indicator of tumor burden and metastasis in patients with malignant diseases.
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PMID:Potential use of soluble CD44 in serum as indicator of tumor burden and metastasis in patients with gastric or colon cancer. 750 22

CD44 is an adhesion molecule that is involved in the progression of several tumor types, including those originating in the intestine. There are several alternatively spliced forms of CD44. Here we show that intestinal epithelial cells express the standard form of CD44 (CD44s). The same form of CD44 is found in IEC-18, a cell line derived from normal rat intestinal crypts. Upon transfection of IEC-18 cells with ras or src, two oncogenes that are frequently activated in intestinal tumors, a significant induction of CD44s is observed. A causal role for ras in this induction is shown by using IEC clones transfected with an inducible ras expression vector. The oncogene-transformed IEC clones display a high degree of hyaluronic acid-dependent cell-cell adhesion that is not observed in the parental IEC-18 cells suggesting that ras- and src-induced overexpression of CD44 can alter the adhesion properties of intestinal cells.
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PMID:Activated ras and src induce CD44 overexpression in rat intestinal epithelial cells. 750 29

Endocrine pancreatic tumors are neuroendocrine neoplasms with malignant potential and give rise to varied clinical syndromes due to excessive secretion of multiple hormones. In this study 22 endocrine pancreatic tumors and 11 carcinoid tumors were examined for the expression of CD44 using a monoclonal antibody. CD44 gene activity of 11 endocrine pancreatic tumor tissues and five carcinoid tumor tissues was also studied by amplifying messenger RNA with the polymerase chain reaction followed by electrophoresis and blot hybridization. Strong immunoreactivity was detected on all gastrinomas examined (P < 0.001), and in two non-functioning endocrine pancreatic tumors. Such immunoreactivity was not observed in other subtypes of endocrine pancreatic tumors. In the normal human pancreas, the acinar portion and ductal epithelial cells stained strongly positive but pancreatic islet cells did not show any significant immunostaining. Furthermore, in endocrine pancreatic tumors with metastatic disease, CD44-positive tumors had a tendency to metastasize to lymph nodes (P = 0.005), as compared with CD44-negative tumors which were locally invasive or metastasized to the liver. Although, in this limited material and short follow-up, we were not able to show any statistical significance, patients with CD44-negative endocrine pancreatic tumors had prolonged survival time compared with patients with CD44-positive tumors (73% versus 59% at 5 years; P = 0.7). Of 10 carcinoid tumors examined, all three foregut carcinoids and one midgut carcinoid stained strongly positive, whereas all other midgut carcinoids were negative. Analysis of CD44 splice variants showed that in all five gastrinomas there was overproduction of alternatively spliced larger molecular variants as compared with other types of endocrine pancreatic tumors and carcinoid tumors. The band pattern from one case of carcinoid tumor with a fulminant clinical course was similar to that of gastrinomas, whereas other carcinoid tumors expressed the epithelial form of CD44. The earlier identified splice variants which confer metastatic behavior on a pancreatic tumor cell line were not expressed in neuroendocrine tumors. Our data indicate that CD44 expression in endocrine pancreatic tumors correlates with the ability to give rise to lymph node metastases and may play a vital role in determining the fate of metastasizing cells. Moreover, because gastrin is not detectable in the normal human pancreas, the pancreatic ductal cell positivity for CD44 strengthened the ductal origin concept of gastrinomas. The band pattern of CD44 splice variants suggests that the previously described splice variants conferring metastatic behavior do not accompany metastatic activity of neuroendocrine tumors.
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PMID:Different splice variants of CD44 are expressed in gastrinomas but not in other subtypes of endocrine pancreatic tumors. 750 23

CD44 is an integral membrane glycoprotein that functions as a receptor for the extracellular matrix glycan, hyaluronan. Here we report that CD44 is a novel biomarker for non-small cell lung tumors, squamous metaplasia of the lung, and activated type II pneumocytes. We have examined the expression of CD44 in 12 human lung tumor cell lines and 23 fixed, paraffin-embedded lung cancers. CD44 transcription and translation is consistently high among non-small cell tumors (5 of 5 cell lines, 10 of 14 tumors) but rare in small cell tumors (1 of 6 cell lines, 0 of 9 tumors). In normal lung, CD44 was confined to the surface of bronchial basal cells and alveolar macrophages. Squamous metaplasia of the lung showed strong CD44 immunoreactivity. Resting type II pneumocytes were largely CD44 negative but rows of active, surfactant-secreting type II cells had significant amounts of CD44 located on lateral surfaces of adjacent cells. The correlation between CD44 and the non-small cell phenotype was further demonstrated in studies of a cultured small cell lung cancer line induced to exhibit characteristics of a non-small lung cancer by infection with v-Ha-ras. Following ras gen insertion, these cells showed a 40-fold increase in CD44 expression. The CD44 detected in lung cancer cells throughout these studies was predominantly the "standard" rather than the "variant" species. Taken together, these results suggest that CD44 is a protein expressed on non-small cell lung tumors, squamous metaplasia, and activated type II cells. In addition, CD44 in cultured small cell lung cancer cells is transcriptionally activated following differentiation by the ras oncogene. The fact that immunohistochemistry can be used to discriminate among the cell types makes CD44 a valuable new marker for lung neoplasia.
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PMID:Expression of CD44 in human lung tumors. 750 20

CD44 is a M(r) 90,000 surface glycoprotein believed to be involved in cell adhesion and migration. We investigated the role of CD44 in tumor growth and metastasis using human melanoma cell lines SMMU-1 and SMMU-2. Both SMMU-1 and SMMU-2 form tumors in the s.c. tissues when injected s.c. in SCID mice but only SMMU-2 metastasizes. Approximately one-half of SCID mice receiving injections of SMMU-2 s.c. develop metastatic tumors. SMMU-2 but not SMMU-1 expresses high levels of the hematopoietic form of CD44 and binds fluorescence-conjugated hyaluronic acid in vitro. GKW.A2 is a monoclonal antibody specific for human CD44 that can completely inhibit the binding of hyaluronic acid to SMMU-2 tumor cells in vitro. Moreover, in vivo injection of GKW.A3 inhibited the growth and metastatic potential of SMMU-2 tumor cells. Administration of GKW.A3 i.v. 1 week after s.c. tumor injection did not inhibit local tumor development but inhibited the formation of metastatic tumors and prolonged animal survival. Therefore, interactions between CD44 on tumor cells and its ligands in vivo may be necessary for tumor growth and metastasis.
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PMID:Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. 751 Oct 44

Variant isoforms of CD44 have been strongly implicated in malignant transformation and cancer metastasis. To ascertain the pattern of expression of these isoforms in human normal, fetal and tumor tissues (breast carcinomas, renal cell carcinomas, malignant melanomas, colon carcinomas, non-Hodgkin-lymphomas, neuroblastomas and brain tumors), we generated monoclonal antibodies against CD44 variant regions. Monoclonal antibodies were produced against variant regions encoded by exons 4v, 6v and 9v. CD44 variant isoforms are expressed on normal epithelial cells in a different pattern. Regions of epithelia that expressed the highest levels of the variant isoforms were those with a high rate of cell division. CD44 variant isoforms were not expressed by all investigated tumors (not by malignant melanomas, brain tumors and neuroblastomas). It is interesting that the expression of CD44 isoforms in non-Hodgkins lymphomas and colon carcinomas shows possibly a correlation with malignancy.
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PMID:[Occurrence of CD44 and its isoforms under orthological and pathological conditions]. 751 Dec 97

CD44 is a widely distributed cell surface glycoprotein which shows heterogeneity in molecular expression as a result of post-translational modification as well as alternative splicing of CD44 mRNA. Functional studies have indicated that CD44 plays a role as an adhesion molecule and that different CD44-expressing cells differ in their capacities for CD44-dependent ligand binding. These observations have raised the possibility that structural modifications of CD44, including those resulting from alternatively spliced mRNA isoforms, are involved in the functional heterogeneity of CD44. To assess the expression of CD44 isoforms in the mouse, we examined CD44 cDNA by reverse transcription polymerase chain reaction (RT-PCR). Southern blotting of PCR products with a CD44 cDNA probe or with internal oligonucleotides revealed the expression in mouse tumor cell lines and normal tissues of multiple CD44 mRNA products which are larger than that observed in the absence of variable exon expression. Interestingly, different mouse tissues, including lymphoid cells, showed unique patterns of alternative CD44 mRNA in Southern blotting analysis. The use of exon-specific primers allowed detection of multiple alternatively spliced mRNA species involving expression of at least seven variable exons. Cloning and sequencing of these PCR products revealed sequence identity with recently identified genomic CD44 sequences and confirmed that the PCR products correspond to mature mRNA expressing alternatively spliced CD44 exons. Taken together, these findings demonstrate that the mouse expresses multiple variably spliced CD44 isoforms and that expression is regulated in a tissue- and cell-type specific manner.
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PMID:CD44 isoform expression mediated by alternative splicing: tissue-specific regulation in mice. 751 28

Identification of antigens by monoclonal antibodies (MAbs) on sections of human melanoma by immunoperoxidase techniques was used to determine whether certain adhesion molecules and "selectin-like" molecules may be related to the metastatic potential of primary melanoma. The adhesion molecules examined were the leukocyte function antigen (LFA-1) and its ligand--intercellular adhesion molecule-1 (ICAM-1), the receptor alpha V beta 3 for vitronectin, its subunits alpha V and beta 3, and the CD36 receptor for thrombospondin (TSP). The criteria used to establish metastatic potential were relation of the molecules to tumor thickness and differences in expression: (i) between radial and vertical growth phases of the primary tumors and (ii) between 34 primary and 21 unrelated metastases. By these criteria ICAM-1, alpha V beta 3 and its subunit were associated with the malignant potential of primary melanoma. These molecules were not expressed on nevi or other skin cancers with low metastatic potential such as squamous (SCC) and basal cell carcinomas (BCC). In contrast, expression of TSP and the CD36 receptor for TSP were not related to metastatic potential. CD36 was expressed widely not only on melanoma but also on BCC, SCC and nevi. Similarly, the selectin-like molecule, CD44, was widely expressed on melanoma and non-melanoma carcinomas. The lymph node homing receptor, Leu 8, and the cutaneous lymphocyte antigen (CLA) were not detected on melanoma. Leu 8 was present on normal epithelium and SCCs, and common leucocyte antigen (CLA) was detected on lymphocytes in the epithelium and near melanoma. These results support previous suggestions that expression of ICAM-1 and V beta 3 integrin or its subunit beta 3 on melanoma may be a useful prognostic marker in primary melanoma. They do not support a role for CD44, Leu 8, CLA and TSP or its receptor CD36 in the metastatic process in melanoma.
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PMID:Immunohistological examination of the relationship between metastatic potential and expression of adhesion molecules and 'selectins' on melanoma cells. 751 76

Local tumor growth has been reported after subcutaneous and intraperitoneal injection of Hodgkin's disease (HD) derived cell lines into different immunodeficient mouse strains. An animal model with disseminated growth of tumor cells would be useful for studying the in vivo biology of HD cells as well as for preclinical testing of new therapeutic regimens. For this purpose the HD-derived cell lines L540, L540cy, L428, and KM-H2 were injected intravenously into SCID mice. In contrast to L428 and KM-H2, widespread neoplasia occurred after a period of four to six weeks following injection of L540 and the subline L540cy. Lymph nodes were found to be the preferred site of tumor growth. CD30 surface antigen expression on Hodgkin cells and the karyotype of the tumor cells were preserved in the animal host. Thus, to a large extent, the SCID mouse model mimics the dissemination pattern of Hodgkin's disease in man. To evaluate the role of adhesion molecule expression in the dissemination of HD-derived cell lines, CD44 and members of the immunoglobulin, integrin, selectin, and Fc receptor families were quantified by flow cytometry. CD30 expression was also measured. Although CD44 expression has been correlated with dissemination in non-Hodgkin's lymphoma (NHL), this was not the case in the Hodgkin's SCID mouse model. CD44 was not expressed on the disseminating cell lines L540 and L540cy but was expressed in the nondisseminating lines L428 and KM-H2.
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PMID:Disseminated growth of Hodgkin's-derived cell lines L540 and L540cy in immune-deficient SCID mice. 751 37

Neoplastic progression of colorectal epithelial cells from benign adenomas to malignant carcinomas appears to result from a series of genetic alterations involving both oncogenes and tumor suppressor genes. This progression was recently found to be associated with expression of splice variant isoforms of CD44, a cell surface hyaluronate receptor implicated in carcinogenesis. In this study we examined the relationship of CD44 expression to somatic genetic events in the adenoma-carcinoma sequence: point mutation of K-ras in codons 12 and 13 and overexpression of p53 protein as a marker of gene mutation. Among 22 small adenomas, CD44 was present in 9 (41%), of which only 1 contained a K-ras mutation. CD44 was absent in the other 2 small adenomas positive for K-ras mutation or p53 overexpression. In contrast to the early expression of CD44 in small adenomas, mutations of K-ras and p53 were detected preferentially in large adenomas and late-stage adenomas containing carcinoma. The frequent expression of CD44 prior to K-ras and p53 gene alterations in colorectal neoplasia suggests that activation of CD44 gene expression is related to earlier events in the adenoma-carcinoma sequence, possibly cell activation and proliferation following APC gene mutation or alteration of DNA methylation.
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PMID:CD44 expression in colorectal adenomas is an early event occurring prior to K-ras and p53 gene mutation. 751 84


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