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

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.