Role of the microenvironment in mantle cell lymphoma: IL-6 is an important survival factor for the tumor cells

Liang Zhang, Jing Yang, Jianfei Qian, Haiyan Li, Jorge E. Romaguera, Larry W. Kwak, Michael Wang, Qing Yi

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma frequently involved in the lymph nodes, bone marrow, spleen, and gastrointestinal tract. We examined the role of IL-6 in MCL. Human MCL cells expressed the membrane gp130 and soluble gp80, and some of them also secreted IL-6. Neutralizing autocrine IL-6 and/or blocking IL-6 receptors in IL-6 +/gp80+ MCL cells inhibited cell growth, enhanced the rate of spontaneous apoptosis, and increased sensitivity to chemotherapy drugs. For IL-6- or gp80low MCL cells, paracrine or exogenous IL-6 or gp80 protected the cells from stress-induced death. Knockdown of gp80 in gp80high MCL cells rendered the cells more sensitive to chemotherapy drugs, even in the presence of exogenous IL-6. In contrast, overexpression of gp80 in gp80low/IL-6+ MCL cells protected the cells from chemotherapy drug-induced apoptosis in vitro and compromised the therapeutic effect of chemotherapy in vivo. IL-6 activated the Jak2/STAT3 and PI3K/Akt pathways in MCL, and the inhibition of these pathways completely or partially abrogated IL-6-mediated protection of MCL cells. Hence, our study identifies IL-6 as a key cytokine for MCL growth and survival and suggests that targeting the IL-6 pathway may be a novel way to improve the efficacy of chemotherapy in MCL patients.

Original languageEnglish (US)
Pages (from-to)3783-3792
Number of pages10
JournalBlood
Volume120
Issue number18
DOIs
StatePublished - Nov 1 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Role of the microenvironment in mantle cell lymphoma: IL-6 is an important survival factor for the tumor cells'. Together they form a unique fingerprint.

Cite this