Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour necrosis factor alpha (TNF) mRNA is detected in the macrophage infiltrate surrounding the tumour, but the cellular/molecular interactions leading to TNF gene expression in macrophages are unknown. The in vitro system in which human blood monocytes are stimulated with human cancer cells for TNF release was used to study such interactions. Monoclonal antibodies (MAbs) against various adhesion molecules (LFA-1, LFA-3, ICAM-1, VNR, VLA beta I chain) were unable to block TNF production in co-culture of monocytes with a human pancreatic carcinoma (HPC) cell line. However, anti-CD44 and anti-HLA-DR MAbs effectively blocked TNF release and TNF-mRNA induction in monocytes. Pre-incubation of monocytes with anti-HLA-DR and tumour cells with anti-CD44 MAbs had a similar effect. It was concluded that CD44 molecules are involved in tumour-monocyte interactions and that HLA-DR determinants of monocytes are engaged in signal transduction for TNF gene activation. These findings may suggest that certain surface determinants of tumour cells act as ligands for MHC class-II molecules and induce TNF production in monocytes.
Int J Cancer 1994 Jan 15
PMID:The MHC class-II and CD44 molecules are involved in the induction of tumour necrosis factor (TNF) gene expression by human monocytes stimulated with tumour cells. 750 90

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.
Cancer Res 1994 Mar 01
PMID:Expression of CD44 in human lung tumors. 750 20

Expression of CD44, the cellular hyaluronate receptor, was examined in human prostate cell lines. CD44 mRNA was detected in cell lines PC3 and DU145, both established from organ metastases of prostate adenocarcinoma, but not in cell line LNCaP, established from a lymph node metastasis. PC3 and DU145, but not LNCaP, are tumorigenic and metastatic in nude mice. Of the CD44 mRNA species identified, the standard CD44s as well as variant isoforms CD44v7, CD44v10, CD44v14, CD44v13-v14, CD44v12-v14 and CD44v7-v14 are represented.
Cancer Lett 1994 Jan 15
PMID:Expression of CD44 in prostate cancer cells. 751 Feb 14

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.
Cancer Res 1994 Mar 15
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

Expression of isoforms of the CD44 hyaluronan receptor/lymph-node endothelial receptor by human tumour cells is thought to play a role in tumour growth and metastasis. These isoforms which vary in the length of the extracellular domain are generated by differential RNA splicing that involves the 10 alternative exons (v1 to v10) encoding the membrane proximal region of the molecule. Several tumours have been shown to over-express CD44 containing the v6 exon, and this, together with other evidence, has led to the suggestion that v6 may play a causative role in tumour metastasis. In this report we have compared the expression of CD44 isoforms between different lung tumour lines, including SCLC, squamous-cell carcinoma, adenocarcinoma and mesothelioma, using both RT-PCR and fluorescent antibody staining with a panel of CD44 exon-specific monoclonal antibodies (MAbs). Our results show large differences in vCD44 expression between individual tumour lines. Little or no vCD44 containing the metastasis-associated v6 exon was detected in most tumours, including the highly metastatic SCLC lines. Indeed, the SCLC lines and some squamous-cell carcinomas contained only very low levels of either vCD44 or CD44H, indicating that CD44 expression may not always correlate with tumour development or dissemination. One of the squamous-cell carcinomas studied (HOTZ) was found to express a complex mixture of CD44 splice variants similar to the immortalized normal bronchial epithelial line BEAS-2B. Cloning and sequencing of vCD44 from the HOTZ cell line yielded several splice variants that have also been identified on leukaemic cells, normal keratinocytes and activated peripheral-blood lymphocytes.
Int J Cancer Suppl 1994
PMID:Expression of alternatively spliced forms of the CD44 extracellular-matrix receptor on human lung carcinomas. 751 25

The CD44 group of transmembrane glycoproteins encompasses several isoforms expressed in a variety of tissues. All isoforms are encoded by the same gene on chromosome 11 and are formed by alternative splicing of their mRNA. CD44 isoforms belong to the family of cell adhesion molecules and to the sub-family of the hyaladherins in consideration of their affinity for hyaluronate and their structural homology with the cartilage link protein. The standard form of CD44, CD44H exhibits a high affinity for hyaluronate, plays a role in the uptake and degradation of this glycosaminoglycan and participates in cell locomotion in its presence. In physiology, CD44H plays a role in the homing of lymphocytes into Peyer's patches, in organogenesis and in the degradation of hyaluronate in lung or lymphoid tissue. In pathology, CD44H probably enhances the tumorigenic properties of some lymphomas and melanomas. The variant form CD44E exhibits low affinity for hyaluronate and its role in cell-cell adhesion in epithelia is suspected. The variant form CD44V (or CD44M) confers metastatic properties to rat carcinoma cells and is expressed in human breast and colorectal cancer and in adenomatous polyps.
Bull Cancer 1993 Oct
PMID:[CD44, the hyaluronic acid cell receptor. Its role in neoplastic invasion and metastatic dissemination]. 751 31

About one in three people in modern industrialised countries die of the consequences of malignant tumours or are found to carry an unsuspected one at the time of autopsy. Early resection of such lesions and appropriate adjuvant therapy is very effective in curing the disease. There is therefore a strong clinical incentive to find effective methods of early diagnosis, assessment of prognosis and treatment of neoplastic lesions and research on this topic is directed at a numerically significant medical problem. Recently it has been found that many human tumours show severe abnormalities in the expression of the CD44 gene which increase with progression to metastatic malignancy. By alternative splicing mechanisms this gene codes for a family of heavily glycosylated cell surface proteins involved in many important cellular activities. In neoplasia there is gross overexpression of various products of the gene associated with disorderly splicing, which can be detected in clinical samples with the sensitive technique of reverse transcription-polymerase chain reaction (RT-PCR). These disturbances begin early in the neoplastic process and can be detected in very small biopsy samples. It has also been shown that it is possible to achieve non-invasive diagnosis of malignancy by analysis of CD44 expression in exfoliated cells in body fluids and waste products. The potential significance of these observations for early diagnosis of symptomatic cancer and for screening of the population for asymptomatic lesions are readily seen and await further investigation. Separate work in our laboratory has succeeded in DNA-mediated transfer of metastatic capability through two rounds of transfection into non-metastatic tumour cells and a metastasis-associated human DNA fragment has been recovered from the transfectants and sequenced. Using primers designed to anneal to a coding region identified by computer analysis within the novel sequence, it has been shown with RT-PCR that it is heavily expressed in metastatic cancer tissues, but not in corresponding normal ones. This could be of value in assessing the prognosis of patients using small biopsy samples from their primary tumours and the potential of this sequence for such purposes and for possible therapeutic intervention is currently being explored. Recent work in several laboratories has shown that elevated expression of certain other specific growth factor genes, including c-met and EGFR, correlates with metastatic capability. Combined evaluation of such markers in further studies will in time give useful information on the prognosis of individual patients to guide therapeutic decisions and the implications of these recent advances for clinical practice and future research are discussed below.
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PMID:Deranged activity of the CD44 gene and other loci as biomarkers for progression to metastatic malignancy. 751 58

Variant CD44 has recently been shown to serve as a metastasis marker in human breast cancer. Certain variant epitopes on primary tumors predict poor survival probabilities for the patients. In this study, immunohistochemical analysis of 16 uterine cervical carcinomas showed strong expression of several CD44 variant epitopes in all samples. In normal cervical epithelia from 5 patients, expression of these epitopes was restricted to particular cell layers, with expression being strong in basal and spinal cells but absent in superficial cells. Fifteen of 16 cancer samples were stained strongly with an antibody which recognizes one particular CD44 epitope that is encoded by both variant exons v7 and v8. This epitope was not detectable in normal cervical epithelium. CD44-mRNA splicing analysis showed qualitative and quantitative differences between malignant and normal tissues with a much more complex splice pattern and high expression of a large CD44 isoform containing variant exons v3 to v10 (including the v7/v8 transition epitope) in about one-half of the cancer samples. Interestingly, patients with lymph node metastases were in this group only. These differences in CD44 epitope expression and mRNA splicing in cervical carcinoma reveal dynamic changes in CD44 expression during carcinogenesis. Such changes could provide metastatic cells with a selective advantage during the carcinogenic process. Furthermore, the v7/v8 epitope may be suitable for screening early stages of cervical cancer.
Cancer Res 1994 Jul 01
PMID:Surface protein expression and messenger RNA-splicing analysis of CD44 in uterine cervical cancer and normal cervical epithelium. 751 19

CD44, a cell surface glycoprotein, is involved in lymphocyte trafficking from the blood to lymphatic tissues, and is of importance in dissemination of lymphoma. A variant form of CD44 that has additional amino acids in the common protein backbone (CD44v6) also seems to play a role in the metastatic dissemination of malignancies. We measured serum CD44 and CD44v6 in 34 patients with lymphoma and in healthy controls by dot blot assay. Small amounts of both CD44 (range, 10 to 80 ng/mL) and CD44v6 could be detected in sera of all controls. Serum CD44 was elevated in all patients with lymphoma before treatment (range, 70 to > 2,000 ng/mL, P < .0001), and CD44v6 was also slightly elevated. Serum CD44 levels correlated with response to treatment. Patients with complete response achieved similar CD44 levels as the controls, whereas those with progressive disease had increased serum CD44 levels. We conclude that both the standard and the variant form of CD44 are detectable in sera of healthy individuals, and that serum CD44 may be useful in monitoring treatment response in patients with lymphoma.
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PMID:Serum CD44 in malignant lymphoma: an association with treatment response. 751 10


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