Expression and role of MIG/CXCR3 axis in mantle cell lymphoma

Exp Cell Res. 2020 Dec 15;397(2):112365. doi: 10.1016/j.yexcr.2020.112365. Epub 2020 Nov 14.

Abstract

Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphoma with a generally aggressive and heterogeneous clinical course. Chemokines are one of the complex components in the tumor microenvironment (TME), and they play a vital role in tumor progression and metastasis. There is no information about the monokine induced by gamma interferon (MIG)/CXC chemokine receptor 3 (CXCR3) axis in patients with MCL. In the present study, we discovered that CXCR3 was highly expressed in MCL tissues and some cell lines including Maver, Z138, and Jeko-1, and significantly associated with clinical factors reflecting high tumor burden in MCL patients. Moreover, elevated serum MIG at diagnosis showed a close relationship with advanced disease and poor prognosis in MCL patients. Additionally, the role of CXCR3 in promoting the proliferation and inhibiting the apoptosis of primary MCL cells and Jeko-1 cells was validated by in vitro experiments. Further research indicated that the MIG/CXCR3 axis mediated MCL cell migration to the TME through the PI3K/AKT signaling pathway. Therefore, the MIG/CXCR3 axis might be a potential target with fewer off-target side effects than other targets in MCL.

Keywords: CXC receptor 3 (CXCR3); Mantle cell lymphoma (MCL); Migration; Monokine induced by gammainterferon (MIG); Prognosis; Tumor microenvironment (TME).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Proliferation
  • Chemokine CXCL9 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphoma, Mantle-Cell / metabolism
  • Lymphoma, Mantle-Cell / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, CXCR3 / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL9
  • Receptors, CXCR3