Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocyte growth factor (HGF)/scatter factor (SF) is the ligand for a tyrosine kinase cell surface receptor encoded by the MET protooncogene (c-MET). HGF/SF can induce proliferation and motility in epithelial cells and promotes invasion of carcinoma cells and NIH3T3 fibroblasts transfected with both HGF/SF and c-MET genes. Our results show that HGF/ SF and c-MET also play a role in adhesion and invasion of human lymphoma cells. c-MET mRNA is expressed in hemopoietic cells, such as hemopoietic progenitor cells (CD34+ cells) in bone marrow (BM) and mobilized peripheral blood, immature B cells in cord blood and BM, and germinal center B-centroblasts. In normal peripheral blood B cells, which are c-MET-, c-MET expression was induced by PMA, ConA, HGF/ SF, and Epstein-Barr virus (EBV) infection. Using immunohistochemistry, we detected c-MET on the cell surface of large activated centroblasts in lymph nodes from patients with B-non-Hodgkin's lymphoma and Hodgkin's disease. In the latter group, c-MET expression correlated well with the presence of EBV. Because HGF/SF and c-MET promote metastasis of carcinoma cells, we studied the effects of c-MET stimulation by HGF/SF of B-lymphoma cells on properties relevant for metastasis, ie, adhesion, migration, and invasion. HGF/SF stimulated adhesion of the c-MET+ B-cell lines to the extracellular matrix molecules fibronectin (FN) and collagen (CN) in a dose dependent manner. However, adhesion to laminin was not affected by HGF/SF. Adhesion to FN was mediated by beta 1-integrins alpha 4 beta 1 (VLA4) and alpha 5 beta 1 (VLA5) since blocking antibodies against beta 1- (CD29), alpha 4-(CD49d), or alpha 5- (CD49e) integrin subunits, completely reversed the effect of HGF/SF. Furthermore, HGF/SF induced adhesion was abrogated by addition of genistein, which blocks protein tyrosine kinases, including c-MET. Addition of HGF/SF resulted in a sixfold increase in migration of c-MET B-lymphoma cells through Matrigel, compared to medium alone. In rat fibroblast cultures, HGF/SF doubled the number of c-MET+ B-lymphoma cells that invaded the fibroblast monolayer. In these adhesion, migration and invasion assays HGF/SF had no effect on c-MET- cell lines. In conclusion, c-MET is expressed or can be induced on immature, activated, and certain malignant B cells. HGF/SF increased adhesion of c-MET+ B-lymphoma cells to FN and CN, mediated via beta 1-integrins alpha 4 beta 1 and alpha 5 beta 1, and furthermore promoted migration and invasion.
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PMID:Hepatocyte growth factor/scatter factor promotes adhesion of lymphoma cells to extracellular matrix molecules via alpha 4 beta 1 and alpha 5 beta 1 integrins. 902 31

The expression of a series of adhesion receptors: L-selectins (CD62L): Leu-8, several integrins (LFA-1: CD11a/CD18, VLA-4: CD49d/CD29 and VLA-5: CD49e/CD29), ICAM-1(CD54) and the 'homing receptor' (CD44) were investigated by a dual color flow cytometry in 56 cases of B cell disorders namely, 39 chronic lymphocytic leukemias (CLL), four hairy cell leukemia (HCL), seven splenic lymphoma with villous lymphocytes (SLVL) and six other non-Hodgkin's lymphoma (NHL). The functional activity of L-selectins was assessed with L-selectin ligand analogs (polyphosphomonester core polysaccharide: PPME and fucoidin). Leukemic B cells were identified with phycoerythrin-conjugated monoclonal antibodies (McAbs) anti-CD19, anti-kappa/lambda investigated simultaneously for the expression of adhesion receptors estimated with fluorescein-isothiocyanate (FITC) conjugated McAbs. The percentage of leukemic cells expressing L-selectins (Leu-8) was high in CLL (52% of positive cases) and integrin expression (LFA-1, VLA-4, 5) was low (19 and 33%, respectively), while a reverse pattern, low Leu-8 (17%), and a high VLA-4 (77%), was observed in non-CLL cases. The expression of LFA-1 alpha-chain was variable in non-CLL cases, and the LFA-1 heterodimer was expressed on most clonal B cell in NHLs (92%). LFA-1 alpha-chain was detected on cells from only one HCL case, while beta2 integrin was regularly expressed on hairy cells. VLA-5 integrin was found on a relatively small number (26%) of mature B cell leukemias. A remarkable finding was the detection of ICAM-1 in all CLL cases albeit the number of positive cells was significantly lower (P < 0.05) compared to non-CLL cases. CD44 was expressed on a high number of neoplastic cells in all the investigated categories. There was no correlation between the expression of the adhesion molecules and clinical and laboratory parameters except for CD18 which was expressed on a significantly (P < 0.05) higher number of leukemic cells in CLL with more advanced stages. This study demonstrates that even closely related B cell leukemia/lymphomas have a certain well defined and strictly variable adhesion profile which is characteristic of the disease entity and therefore, the adhesion profile may offer additional information useful for differential diagnosis and study of disease pathogenesis.
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PMID:Adhesion receptors on peripheral blood leukemic B cells. A comparative study on B cell chronic lymphocytic leukemia and related lymphoma/leukemias. 906 81

The yield of CD34+ PBPC and colony-forming units-granulocyte-macrophage (CFU-GM) in leukapheresis products and the expression of the adhesion molecules CD11a, CD31, CD49d, CD49e, CD54, CD58, CD62L, c-kit (CD117), Thy-1 (CD90), CD33, CD38, and HLA-DR on CD34+ PBPC were analyzed in patients with cancer of the testis (n = 10), breast cancer (n = 10), Hodgkin's disease (n = 20), high-grade (n = 20) and low-grade (n = 20) non-Hodgkin's lymphoma, and healthy donors (n = 20) undergoing G-CSF (filgrastim)-stimulated PBPC mobilization. For each disease entity, G-CSF was administered in two different doses, 10 microg G-CSF/kg body weight (BW)/day s.c. vs. 24 microg G-CSF/kg BW s.c./day in steady-state condition. Data were compared for each dose group separately. Patients with cancer of the testis and breast cancer mobilized significantly more CD34+ cells than patients with high-grade and low-grade non-Hodgkin's lymphoma and Hodgkin's disease (p<0.05). Correspondingly, expression of CD49d on CD34+ PBPC was significantly lower in the same patients with cancer of the testis compared with high-grade and low-grade non-Hodgkin's lymphoma and Hodgkins' disease and in patients with breast cancer compared with high-grade and low-grade non-Hodgkin's lymphoma, Hodgkins's disease, and healthy donors. Similar results were obtained for CD49e. These data suggest that the expression of the adhesion molecules CD49d and CD49e on G-CSF-mobilized CD34+ cells of patients with solid tumors, non-Hodgkin's lymphoma, Hodgkin's disease, and healthy donors is inversely correlated with the amount of mobilized CD34+ cells.
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PMID:Expression of the adhesion molecules CD49d and CD49e on G-CSF-mobilized CD34+ cells of patients with solid tumors or non-Hodgkin's and Hodgkin's lymphoma and of healthy donors is inversely correlated with the amount of mobilized CD34+ cells. 1079 4

We analyzed the expression pattern of adhesion molecules including beta 1-integrins (CD49c, CD49d, CD49e, CD49f), beta 2-integrins (CD11a, CD11b, CD11c), CD44, and CD54 in 141 children with B-cell precursor acute lymphoblastic leukemia (pre-B ALL) and in 21 children with B-cell ALL/non-Hodgkin's lymphoma (B-ALL/NHL). The frequencies of CD11a, CD49f, and CD44 expression were significantly higher in CD34+ pre-B ALL than in CD34- pre-B ALL. Although CD49d, CD49e, and CD44 were less frequently expressed in B-ALL/NHL than in pre-B ALL, the expression of CD11a and CD54 were more frequent in B-ALL/NHL. In pre-B ALL, expression of CD11a positively correlated with that of CD11b (P < .05) and CD54 (P < .01), and CD49c positively correlated with CD49f (P < .01). Of the clinical parameters of patients with pre-B ALL, expression of CD11a was associated with a low leukocyte count (P < .05). The presence of CD54 on the cell surface was an independent factor indicating a poor prognosis. The estimated 5-year event-free survival was 42.3% for CD54+ (n = 31) compared with 70.3% for CD54- patients (n = 38) (P < .05). These findings demonstrated that expression of adhesion molecules is dependent on the phenotype of B-lineage cells and that the expression of some of these molecules has clinical significance.
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PMID:Expression of adhesion molecules in childhood B-lineage-cell neoplasms. 1097 12