The tyrosine kinase receptor Met and its ligand HGF are co-expressed and functionally active in HHV-8 positive primary effusion lymphoma
| Autor: | Enzo Medico, Alessia Carbone, Maria Prat, Gianluca Gaidano, Annunziata Gloghini, Daniela Buonaiuto, Giuseppe Saglio, Lucia Fassone, Daniela Vivenza, Gian Carlo Avanzi, Daniela Capello, Margherita Gallicchio |
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| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
Cell type Lymphoma B-Cell Biology Receptor tyrosine kinase chemistry.chemical_compound immune system diseases hemic and lymphatic diseases Tumor Cells Cultured medicine Humans RNA Messenger B cell integumentary system Hepatocyte Growth Factor Reverse Transcriptase Polymerase Chain Reaction virus diseases Tyrosine phosphorylation Herpesviridae Infections Hematology Proto-Oncogene Proteins c-met medicine.disease Immunohistochemistry Lymphoma Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology chemistry Cell culture Herpesvirus 8 Human Immunology Cancer research biology.protein Hepatocyte growth factor Primary effusion lymphoma medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/sj.leu.2401666 |
| Popis: | Primary effusion lymphoma (PEL) harbors consistent infection by human herpesvirus-8, preferentially develops in immunodeficient patients and selectively localizes to the serous body cavities. Histogenetic analysis has suggested that PEL originates from post-germinal center, pre-terminally differentiated B cells sharing phenotypic features with plasma cells. Here we have investigated the expression status and functional integrity of the Met tyrosine kinase receptor and of its ligand hepatocyte growth factor (HGF). Thirteen PEL (nine cell lines and four primary specimens) were analyzed for Met and HGF expression and function by multiple assays. For comparison, a panel of 34 high grade B cell non-Hodgkin lymphomas (NHL) other than PEL was also investigated. Co-expression of Met and HGF was found in all PEL analyzed, whereas it was restricted to 1/34 B cell NHL other than PEL (P < 0.001; chi2 test). The Met protein expressed by PEL displays biochemical characteristics typical of Met expressed by other cell types and is capable of tyrosine autophosphorylation. By using a combination of immunological and biological assays, production and secretion of a functional HGF species was identified in all PEL cell lines analyzed. HGF stimulation of PEL cells rapidly induces Met tyrosine phosphorylation, demonstrating the functional integrity of the Met/HGF loop. Because of the well known mitogenic and motogenic properties of Met/HGF interactions, these data may bear implications for PEL growth and dissemination. Among B cell neoplasms, Met/HGF co-expression selectively clusters with PEL and, as demonstrated by previous studies, with multiple myeloma plasma cells, thus reinforcing the notion that PEL displays biologic similarities with tumors derived from late stages of B cell differentiation. |
| Databáze: | OpenAIRE |
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