Histamine-releasing factor/translationally controlled tumor protein plays a role in induced cell adhesion, apoptosis resistance and chemoresistance in non-Hodgkin lymphomas

Abstract

Mounting evidence has proved that cellular adhesion confers resistance to chemotherapy in multiple lymphomas. The molecular mechanism underlying cell adhesion-mediated drug resistance (CAM-DR) is, however, poorly understood. In this study, we investigated the expression and biologic function of histamine-releasing factor (HRF) in non-Hodgkin lymphomas (NHLs). Clinically, by immunohistochemistry analysis we observed obvious up-regulation of HRF in NHLs including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and natural killer (NK)/T-cell lymphoma. Functionally, overexpression and knockdown of HRF demonstrated the antiapoptotic effect of HRF in NHL cells, which may be associated with activation of the p-CREB/BCL-2 signaling pathway. Moreover, cell adhesion assay demonstrated that adhesion to fibronectin (FN) or HS-5 up-regulated HRF expression, while knockdown of HRF resulted in decreased cell adhesion, which led to reversed CAM-DR. Our finding supports the role of HRF in NHL cell apoptosis, adhesion and drug resistance, and may provide a clinical therapeutic target for CAM-DR in NHL.

Keywords::

• Non-Hodgkin lymphoma (NHL)
• HRF
• immunohistochemistry
• apoptosis
• cell adhesion
• CAM-DR

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81172879, No. 81201858, No. 81372537); Natural Scientific Foundation of Jiangsu Province Grant (No. BK2012231); and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Potential conflict of interest

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