GLI2 transcription factor mediates cytokine cross-talk in the tumor microenvironment

Sherine F. Elsawa, Luciana L. Almada, Steven C. Ziesmer, Anne J Novak, Thomas Elmer Witzig, Stephen Maxted Ansell, Martin E Fernandez-Zapico

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Tumor cells interact with their surrounding microenvironment to survive and persist within the host. Cytokines play a key role in regulating this crosstalk between malignant cells and surrounding cells in the microenvironment. Although this phenomenon is clearly established, the molecular mechanisms mediating this cellular event remain elusive. Here, using as a model bone marrow stromal cells, we describe a novel signaling mechanism initiated by CCL5 in these cells leading to up-regulation of immunoglobulin secretion by malignant B cells. CCL5 increases IL-6 expression and secretion in bone marrow stromal cells. IL-6 in turn induces Ig secretion by malignant B cells. Analysis of the mechanism reveals that CCL5 signaling induces GLI2 through a PI3K-AKT-IκBα-p65 pathway and requires GLI2 transcriptional activity to modulate IL-6 expression and Ig secretion in vitro and in vivo. Together, these results identify a novel signaling pathway mediating the stromal-cancer cell interactions, leading to increased Ig production by malignant cells.

Original languageEnglish (US)
Pages (from-to)21524-21534
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number24
DOIs
StatePublished - Jun 17 2011

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Tumor Microenvironment
Tumors
Transcription Factors
Cells
Cytokines
Interleukin-6
Mesenchymal Stromal Cells
Bone
B-Lymphocytes
Cellular Microenvironment
Stromal Cells
Crosstalk
Phosphatidylinositol 3-Kinases
Cell Communication
Immunoglobulins
Neoplasms
Up-Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

GLI2 transcription factor mediates cytokine cross-talk in the tumor microenvironment. / Elsawa, Sherine F.; Almada, Luciana L.; Ziesmer, Steven C.; Novak, Anne J; Witzig, Thomas Elmer; Ansell, Stephen Maxted; Fernandez-Zapico, Martin E.

In: Journal of Biological Chemistry, Vol. 286, No. 24, 17.06.2011, p. 21524-21534.

Research output: Contribution to journalArticle

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