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

D. Capello, G. Gaidano, M. Gallicchio, A. Gloghini, E. Medico, D. Vivenza, D. Buonaiuto, L. Fassone, G. C. Avanzi, G. Saglio, M. Prat, A. Carbone

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 (P <0.001; χ2 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.

Original languageEnglish
Pages (from-to)285-291
Number of pages7
JournalLeukemia
Volume14
Issue number2
Publication statusPublished - 2000

Fingerprint

Primary Effusion Lymphoma
Human Herpesvirus 8
Hepatocyte Growth Factor
Receptor Protein-Tyrosine Kinases
Ligands
B-Lymphocytes
B-Cell Lymphoma
Plasma Cells
Non-Hodgkin's Lymphoma
Tyrosine
Cell Line
Germinal Center
Multiple Myeloma
Biological Assay

Keywords

  • AIDS
  • HGF
  • Lymphoma
  • Met
  • Post-transplant
  • Primary effusion lymphoma

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

Cite this

The tyrosine kinase receptor Met and its ligand HGF are co-expressed and functionally active in HHV-8 positive primary effusion lymphoma. / Capello, D.; Gaidano, G.; Gallicchio, M.; Gloghini, A.; Medico, E.; Vivenza, D.; Buonaiuto, D.; Fassone, L.; Avanzi, G. C.; Saglio, G.; Prat, M.; Carbone, A.

In: Leukemia, Vol. 14, No. 2, 2000, p. 285-291.

Research output: Contribution to journalArticle

Capello, D, Gaidano, G, Gallicchio, M, Gloghini, A, Medico, E, Vivenza, D, Buonaiuto, D, Fassone, L, Avanzi, GC, Saglio, G, Prat, M & Carbone, A 2000, 'The tyrosine kinase receptor Met and its ligand HGF are co-expressed and functionally active in HHV-8 positive primary effusion lymphoma', Leukemia, vol. 14, no. 2, pp. 285-291.
Capello, D. ; Gaidano, G. ; Gallicchio, M. ; Gloghini, A. ; Medico, E. ; Vivenza, D. ; Buonaiuto, D. ; Fassone, L. ; Avanzi, G. C. ; Saglio, G. ; Prat, M. ; Carbone, A. / The tyrosine kinase receptor Met and its ligand HGF are co-expressed and functionally active in HHV-8 positive primary effusion lymphoma. In: Leukemia. 2000 ; Vol. 14, No. 2. pp. 285-291.
@article{a19b9db6370b4e399c53ba6397bc923b,
title = "The tyrosine kinase receptor Met and its ligand HGF are co-expressed and functionally active in HHV-8 positive primary effusion lymphoma",
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 (P <0.001; χ2 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.",
keywords = "AIDS, HGF, Lymphoma, Met, Post-transplant, Primary effusion lymphoma",
author = "D. Capello and G. Gaidano and M. Gallicchio and A. Gloghini and E. Medico and D. Vivenza and D. Buonaiuto and L. Fassone and Avanzi, {G. C.} and G. Saglio and M. Prat and A. Carbone",
year = "2000",
language = "English",
volume = "14",
pages = "285--291",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - The tyrosine kinase receptor Met and its ligand HGF are co-expressed and functionally active in HHV-8 positive primary effusion lymphoma

AU - Capello, D.

AU - Gaidano, G.

AU - Gallicchio, M.

AU - Gloghini, A.

AU - Medico, E.

AU - Vivenza, D.

AU - Buonaiuto, D.

AU - Fassone, L.

AU - Avanzi, G. C.

AU - Saglio, G.

AU - Prat, M.

AU - Carbone, A.

PY - 2000

Y1 - 2000

N2 - 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; χ2 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.

AB - 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; χ2 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.

KW - AIDS

KW - HGF

KW - Lymphoma

KW - Met

KW - Post-transplant

KW - Primary effusion lymphoma

UR - http://www.scopus.com/inward/record.url?scp=0033972570&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033972570&partnerID=8YFLogxK

M3 - Article

VL - 14

SP - 285

EP - 291

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 2

ER -