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)

Tumor growth is dependent in part on interactions between tumor cells and the extracellular matrix of host tissues. Expression of the cell surface glycoprotein CD44/Pgp-1, which mediates cell-substrate interactions is increased in many types of malignancies, but the role of CD44 in tumor growth is largely undefined. Recently, two isoforms of CD44 have been identified: an 80-90 kD form, which has high affinity for cell bound hyaluronate and a 150 kD form which does not mediate attachment to hyaluronate-coated surfaces. In this work, human B cell lymphoma cells stably transfected with cDNA clones encoding either of the two CD44 isoforms were compared for tumorigenicity and metastatic potential in nude mice. Expression of the 80-90 kD form but not the 150 kD form of CD44 greatly enhanced both local tumor formation and metastatic proclivity of the lymphoma cells. Our results suggest that CD44 polypeptides may play an important role in regulating primary and metastatic tumor development in vivo.
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PMID:Distinct effects of two CD44 isoforms on tumor growth in vivo. 191 39

Adhesive interactions between lymphocyte cell-surface receptors and components of the vascular endothelium and the extracellular matrix play an important role in the control of lymphocyte migration and homing. To investigate whether lymphocyte adhesion molecules involved in the migration of normal lymphocytes, i.e., CD44 homing receptor, LFA-1 (CD11a/18), and ICAM-1 (CD54), also play a role in the spread and hence in the disease course of non-Hodgkin's lymphomas (NHL), expression of these molecules was examined in 78 cases of diffuse large-cell lymphoma. Other potential risk factors considered in this study were sex, age, primary tumor localization, lineage (T cell vs. B cell), and histopathological subtype. 27 of 53 (51%) patients with a lymphoma having a high CD44 antigen expression showed tumor spread beyond stage II at diagnosis while this was the case in only three of 25 (12%) patients with lymphomas that were CD44 low/negative (chi-square 25.4, p less than 0.001). Similarly, poor response to treatment, i.e., absence of remission or relapse, and or death from lymphoma, was more common among patients with lymphomas expressing high levels of CD44; actuarial survival among patients with CD44 high and low lymphomas was 47% and 91%, respectively (Mantel-Cox 6.1, p = 0.02). Neither LFA-1 nor ICAM-1 expression showed a significant correlation to lymphoma dissemination or disease course. Of the other factors considered, T cell phenotype was associated with an unfavorable prognosis while nodal localization was a risk factor for dissemination. Taken together, our findings suggest that CD44 antigen expression plays an important role in the dissemination of NHL and via this mechanism exerts an unfavorable prognostic influence.
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PMID:Adhesion molecules in the prognosis of diffuse large-cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD54). 197 38

This review will discuss a number of specific cell adhesion molecules present on the surface of endothelial and epithelial cells in the lung. Molecules such as integrins, proteoglycans, and the hyaluronic acid receptor, CD44, are found on the abluminal or basement membrane side of the cell and function as cell-substratum receptors. Cadherins, integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are present at the cell-cell borders of adjacent endothelial and/or epithelial cells and function to initiate or maintain cell-cell adhesion. Finally, a number of inducible cell adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (ELAM-1), granule-associated membrane protein 140 (GMP140), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are expressed on the luminal surfaces of these cells during inflammation and function as cell-cell adhesion molecules important in white blood cell, platelet, or tumor cell adhesion. These adhesion molecules likely play important roles in maintaining the normal structure and function of the lung, as well as participating in pulmonary processes such as inflammation, wound healing, and the development and spread of malignant disease.
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PMID:Endothelial and epithelial cell adhesion molecules. 200 Dec 88

The influence of 4 murine monoclonal antibodies (MAbs) directed against surface determinants of a metastasizing rat adenocarcinoma (BSp73ASML) on metastatic spread was evaluated and compared to their in vivo binding as well as to the induction of a humoral anti-MAb response, especially with respect to the development of anti-idiotypic (ID) antibodies of the internal image type. In a protocol of explicit immunization, all 4 MAbs transiently inhibited metastatic growth. Survival was prolonged only with one MAb (4.4ASML). With another MAb (1.1ASML), directed against a new variant form of CD44, metastatic growth was accelerated after transient retardation. Retardation of metastatic growth correlated with the humoral anti-MAb response. This accounted for the isotype- as well as for the idiotype-specific response. An exception was noted after immunization with MAb 1.1ASML. Rats with high levels of anti-1.1ASML antibodies, which inhibited binding to the tumor cells (internal image-type antibodies) showed accelerated metastatic spread. Data are interpreted to mean that MAb-induced inhibition of metastatic spread may be based on 2 independent mechanisms: blockade of metastasis-associated epitopes (i.e., with MAb 1.1ASML) and induction of an anti-mouse Ig response. In the latter case it was irrelevant whether the response was isotype- or idiotype-specific.
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PMID:Retardation of metastatic tumor growth after immunization with metastasis-specific monoclonal antibodies. 222 20

In the present study we have identified and characterized three subpopulations of peripheral blood NK cells based on the surface expression of CD56 and CD16. We have designated these subsets CD16neg, CD16dim, and CD16bright according to the relative surface density of CD16. The CD16bright subset comprised about 10% to 15% of PBL, whereas the CD16dim and CD16neg subsets comprise less than 1% of the total lymphocytes. A detailed characterization of these subsets revealed both similarities and differences. The three subsets shared a great deal of phenotypic similarity, expressing CD2, CD7, CD11b, CD38, CD45R, CD18, and the p75 IL-2R on the majority of the cells in each subset. There were, however, several prominent phenotypic differences, particularly in the expression of CD57, CD11c, CD44, CD25, Leu-8, L263, and L265. The CD16neg cells were morphologically large agranular lymphocytes and demonstrated low levels of non-MHC restricted cytolysis of NK-sensitive tumor lines. The CD16dim and CD16bright subsets were large granular lymphocytes and revealed potent cytotoxicity against NK-sensitive targets. All subsets demonstrated IL-2-dependent activation and proliferation; however, the CD16dim and CD16neg subsets were preferentially responsive to very low concentrations of rIL-2. Although rIL-4 effectively inhibited the IL-2-induced cytolytic activation of all three NK cell subsets, only the CD16bright cells showed rIL-4 inhibition of IL-2 dependent proliferation. Cytokine transcription was also differentially regulated in the NK cell subsets after rIL-2 activation. Although TNF-alpha was equally transcribed in each subsets, IFN-gamma and serine protease-HF were preferentially transcribed in the CD16bright NK cells. Based on these results, we propose that these NK cell subsets represent portions of the NK cell differentiation pathway present in the peripheral blood.
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PMID:Comparative studies of human FcRIII-positive and negative natural killer cells. 253 Feb 73

In order to investigate the importance of cell adhesion molecules (CAMs) in renal cell carcinoma (RCC), a cell line, designated as CCF-RC7, was established from a human RCC of the clear cell type. CCF-RC7 was passaged over 50 times in vitro for 3 1/2 years. The cell line has an epithelial morphology and a doubling time of 30 h, forming colonies in soft agar with an average efficiency of 10.4% and producing clear cell tumors in athymic nude mice. CCF-RC7 cells have an aneuploid-hypotetraploid karyotype with a modal chromosome number of 82 and rearrangements in chromosomes 9, 12 and 14. Immunohistochemical and flow immunocytometric analyses revealed high expression of ICAM-1 (CD54), and Hermes antigen (CD44), which was significantly upregulated by cytokine and PMA treatment. VLA-4 was expressed on approximately 20% of tumor cells and could not be altered by cytokine or PMA stimulation. High expression of sialyl Lewis X was also demonstrated by immunohistological examination. This newly characterized cell line will serve as a useful model for the study of CAMs during hematogenous metastasis and host defense mechanisms in human RCC.
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PMID:Expression of cell adhesion molecules in an established and characterized new human renal cell cancer line, CCF-RC7. 748 44

Peptides of melanosomal proteins have recently been shown to be recognized in an HLA-restricted mode by specific cytolytic T lymphocytes in melanoma patients. Dendritic antigen-presenting cells (DC) are considered to be the most effective stimulators of T cell responses, and the use of these cells has therefore been proposed to generate therapeutic responses to tumor antigens in cancer patients. We, therefore, generated DC from peripheral blood of normal donors in the presence of granulocyte/macrophage colony-stimulating factor and interleukin-4. Flow cytometric analysis of the cells during a 2-week culture revealed a loss of CD14 and CD34 expression, a concomittent increase of CD1a, CD11a,b and c, CD44, CD45, CD54, HLA-class I and II, and intermediate levels of CD26, CD80 and CD86. Cultured DC stimulated proliferation of allogeneic T cells and induced a marked, up to 20-fold, stimulation of T cell proliferation after pulsing with tetanus toxoid. To achieve independence of already-identified antigenic peptides presented in HLA class I-restricted fashion, which limits the general applicability of such peptides for vaccination of melanoma patients, we tested whether DC are transfectable with eukaryotic expression plasmids. DC transfected with two reporter genes (CAT, beta-galactosidase) using a liposome-based transfection technique, exhibited only low levels of enzymatically active proteins, but were able to degrade rapidly intracellular proteins and to process peptides efficiently. Chloramphenicol acetyltransferase as well as tyrosinase mRNA were detectable after transfection by reverse-transcriptase-polymerase chain reaction, and enzyme activities became measurable. Furthermore, DC transfected with the tyrosinase gene were able to induce specific T cell activation in vitro, indicating appropriate peptide processing and presentation in DC after transfection. These data suggest new approaches to future tumor vaccination strategies.
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PMID:Dendritic cells generated from peripheral blood transfected with human tyrosinase induce specific T cell activation. 748 49

The A6H mAb raised primarily against human renal cell carcinoma (RCC) has previously been shown to bind strongly to RCC, to some degree to colon carcinoma but only marginally to a variety of normal tissues. Immunohistochemical analysis or RCC tissues containing tumor-infiltrating lymphocytes revealed that A6H stained both tumor cells and lymphocytes. FACS analysis of human peripheral blood cells demonstrated that A6H stained both tumor cells and lymphocytes. FACS analysis of human peripheral blood cells demonstrated that A6H mAb stained 85-90% of both CD4+ and CD8+ T cells, but not granulocytes, monocytes, NK cells or B cells. Furthermore, 85-90% of naive and memory T helper cells were stained with A6H suggesting that the A6H mAb defines unique subsets within these T cell populations. Dual staining showed that A6H mAb bind to an antigen that is clearly distinct from other cell surface molecules on T cells, including CD28, CD29, CD26, CD44 and ICAM-2. A6H mAb binding induced a second signal in anti-CD3 mAb activated T cells, resulting in cell proliferation, IL-2 receptor expression and vigorous production of IFN-gamma and TNF, and production of minor amounts of IL-2. Immunoprecipitation with A6H mAb indicated a molecular weight of 120-140 kDa on both T cells and RCC. We suggest that the A6H mAb defines a unique T cell surface antigen which is involved in signal transduction and is expressed on subsets of human T cells. The co-expression of A6H on T cells and tumor cells suggests a possible function related to common properties of these cells.
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PMID:A novel co-stimulatory T cell antigen co-expressed on renal cell carcinoma. 749 50

A recently described splice variant of CD44 has been shown to confer metastatic potential to non-metastasizing rat pancreatic carcinoma and sarcoma cell lines. Using antibodies raised against a bacterial fusion protein encoded by variant CD44 sequences, we have explored the expression of variant CD44 glycoproteins in human lymphoid cells and tissues, in non-Hodgkin's lymphomas, and in colorectal neoplasia. Normal lymphohematopoietic cells express barely detectable low levels of variant CD44 glycoproteins, while T lymphocytes, upon activation by mitogen or antigen, transiently upregulate expression of specific CD44 variant glycoproteins. The reaction pattern of various antibodies indicates that these CD44 variants contain the domain encoded by exon v6, which is part of the variant that in the rat confers metastatic capability. Interestingly, overexpression of v6 was also found in several aggressive, but not in low-grade, non-Hodgkin's lymphomas (NHL). In human colorectal neoplasia we also observed strong overexpression of CD44 splice variants in all invasive carcinomas and carcinoma metastasis. Interestingly, focal expression was already observed in adenomatous polyps, expression being related to areas of dysplasia. The findings establish CD44 variants as tumor progression markers in colorectal cancer.
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PMID:CD44 splice variants: expression during lymphocyte activation and tumor progression. 750 54

CD44 is a transmembrane glycoprotein involved in the interaction between cells and extracellular matrix. Several variant forms of CD44 exist, which differ from each other in the composition of both the intra- and extracellular domain of the protein. Post-translational modification and alternative RNA processing are responsible for this variation. Recently, it was found that certain variant CD44 proteins, containing extra sequences in the extracellular domain of the protein, are involved in metastatic spread of tumor cells. Variant CD44 proteins are also involved in immunological functions of T and B cells. A large variety of alternatively spliced CD44 mRNAs can be expressed by cells. We have developed a method for the analysis of CD44 mRNAs present in the cell. This reverse transcription-polymerase chain reaction (RT-PCR)-based method can be used to analyze the exon composition of each major CD44 mRNA species present in the cell. In this study we describe the analysis of CD44 mRNAs isolated from six different human cell lines.
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PMID:A PCR-based method for the analysis of human CD44 splice products. 750 77


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