HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration

Xiaoqing Lu, Jun Chen, Raquel Malumbres, Elena Cubedo Gil, David M. Helfman, Izidore Lossos

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

HGAL is a newly identified germinal center (GC)-specific gene whose expression by the tumor cells correlates with a favorable prognosis in patients with diffuse large B-cell and classical Hodgkin lymphomas. The function of HGAL is unknown. Previous studies demonstrated that HGAL is dispensable for GC formation, immunoglobulin gene class-switch recombination, and somatic hypermutation. Herein, we identify a role for HGAL in the regulation of cell motility. We demonstrate that IL-6 induces the phosphorylation of the C-terminal tyrosine residue of the HGAL protein via the Lyn kinase, and promotes its relocalization from the cytoplasm to podosome-like structures. Further, IL-6-induced HGAL phosphorylation increases its interaction with myosin II and is associated with inhibition of cell migration. Knockdown of endogenous HGAL ameliorates IL-6-induced inhibition of cell migration, whereas overexpression of HGAL imparts inhibitory effects of IL-6 on cell migration. Taken together, our results suggest that HGAL is involved in negative regulation of lymphocyte migration, thus constraining lymphocytes to the GC. Inhibition of lymphocyte migration might contribute to the less aggressive clinical behavior of HGAL-expressing lymphomas.

Original languageEnglish
Pages (from-to)4268-4277
Number of pages10
JournalBlood
Volume110
Issue number13
DOIs
StatePublished - Dec 15 2007

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Biomarkers
Cytoskeleton
Cell Movement
Germinal Center
Interleukin-6
Lymphoma
Cells
Cell Migration Inhibition
Lymphocytes
Phosphorylation
Myosin Type II
Immunoglobulin Genes
Immunoglobulin Isotypes
Hodgkin Disease
Genetic Recombination
Tyrosine
Cytoplasm
B-Lymphocytes
Phosphotransferases
Gene expression

ASJC Scopus subject areas

  • Hematology

Cite this

HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration. / Lu, Xiaoqing; Chen, Jun; Malumbres, Raquel; Gil, Elena Cubedo; Helfman, David M.; Lossos, Izidore.

In: Blood, Vol. 110, No. 13, 15.12.2007, p. 4268-4277.

Research output: Contribution to journalArticle

Lu, Xiaoqing ; Chen, Jun ; Malumbres, Raquel ; Gil, Elena Cubedo ; Helfman, David M. ; Lossos, Izidore. / HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration. In: Blood. 2007 ; Vol. 110, No. 13. pp. 4268-4277.
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abstract = "HGAL is a newly identified germinal center (GC)-specific gene whose expression by the tumor cells correlates with a favorable prognosis in patients with diffuse large B-cell and classical Hodgkin lymphomas. The function of HGAL is unknown. Previous studies demonstrated that HGAL is dispensable for GC formation, immunoglobulin gene class-switch recombination, and somatic hypermutation. Herein, we identify a role for HGAL in the regulation of cell motility. We demonstrate that IL-6 induces the phosphorylation of the C-terminal tyrosine residue of the HGAL protein via the Lyn kinase, and promotes its relocalization from the cytoplasm to podosome-like structures. Further, IL-6-induced HGAL phosphorylation increases its interaction with myosin II and is associated with inhibition of cell migration. Knockdown of endogenous HGAL ameliorates IL-6-induced inhibition of cell migration, whereas overexpression of HGAL imparts inhibitory effects of IL-6 on cell migration. Taken together, our results suggest that HGAL is involved in negative regulation of lymphocyte migration, thus constraining lymphocytes to the GC. Inhibition of lymphocyte migration might contribute to the less aggressive clinical behavior of HGAL-expressing lymphomas.",
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AU - Lu, Xiaoqing

AU - Chen, Jun

AU - Malumbres, Raquel

AU - Gil, Elena Cubedo

AU - Helfman, David M.

AU - Lossos, Izidore

PY - 2007/12/15

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N2 - HGAL is a newly identified germinal center (GC)-specific gene whose expression by the tumor cells correlates with a favorable prognosis in patients with diffuse large B-cell and classical Hodgkin lymphomas. The function of HGAL is unknown. Previous studies demonstrated that HGAL is dispensable for GC formation, immunoglobulin gene class-switch recombination, and somatic hypermutation. Herein, we identify a role for HGAL in the regulation of cell motility. We demonstrate that IL-6 induces the phosphorylation of the C-terminal tyrosine residue of the HGAL protein via the Lyn kinase, and promotes its relocalization from the cytoplasm to podosome-like structures. Further, IL-6-induced HGAL phosphorylation increases its interaction with myosin II and is associated with inhibition of cell migration. Knockdown of endogenous HGAL ameliorates IL-6-induced inhibition of cell migration, whereas overexpression of HGAL imparts inhibitory effects of IL-6 on cell migration. Taken together, our results suggest that HGAL is involved in negative regulation of lymphocyte migration, thus constraining lymphocytes to the GC. Inhibition of lymphocyte migration might contribute to the less aggressive clinical behavior of HGAL-expressing lymphomas.

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