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Lymphoma

The tyrosine kinase receptor Met and its ligand HGF are co-expressed and functionally active in HHV-8 positive primary effusion lymphoma

Leukemia volumeĀ 14,Ā pages 285ā€“291 (2000)Cite this article

Abstract

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 (Pā€‰<ā€‰0.001; Ļ‡2 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.

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Acknowledgements

This work was supported by ISS, Programma nazionale sull'AIDS, Progetto ā€˜Patologia, clinica e terapia dell'AIDSā€™, Rome, Italy; by ā€˜Fondazione CRTā€™, Torino, Italy; and by ā€˜Fondazione Piera, Pietro e Giovanni Ferreroā€™, Alba, Italy. DC is being supported by a fellowship from AIRC, Milan, Italy.

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  1. G Gaidano and M Prat: These authors contributed equally to this manuscript

Authors and Affiliations

  1. Division of Internal Medicine, Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

    D Capello,Ā G Gaidano,Ā M Gallicchio,Ā D Vivenza,Ā D Buonaiuto,Ā L FassoneĀ &Ā GC Avanzi

  2. Division of Pathology, Centro di Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori, Aviano, Italy

    A GloghiniĀ &Ā A Carbone

  3. IRCC, University of Torino, Candiolo, Italy

    E Medico

  4. Division of Internal Medicine and Hematology, Department of Clinical and Biological Sciences, University of Torino, Orbassano, Torino, Italy

    G Saglio

  5. Division of Histology, Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

    M Prat

  6. These authors contributed equally to this manuscript,

    G Gaidano,Ā M PratĀ &Ā A Carbone

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Capello, D., Gaidano, G., Gallicchio, M. et al. The tyrosine kinase receptor Met and its ligand HGF are co-expressed and functionally active in HHV-8 positive primary effusion lymphoma. Leukemia 14, 285ā€“291 (2000). https://doi.org/10.1038/sj.leu.2401666

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