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Lymphoma

Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib

Leukemia volume 26, pages 2269–2276 (2012)Cite this article

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Abstract

Hodgkin's lymphoma is frequently associated with mast cell infiltration that correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear. Here, we report that mast cells promote the growth of Hodgkin's tumor by modifying the tumor microenvironment. A transplantation assay shows that primary murine mast cells accelerate tumor growth by established Hodgkin's cell lines, and promote marked neovascularization and fibrosis. Both mast cells and Hodgkin's cells were sensitive to bortezomib, but mast cells were more resistant to bortezomib. However, bortezomib inhibited degranulation, PGE2-induced rapid release of CCL2, and continuous release of vascular endothelial growth factor-A from mast cells even at the concentration that did not induce cell death. Bortezomib-treated mast cells lost the ability to induce neovasculization and fibrosis, and did not promote the growth of Hodgkin tumor in vivo. These results provide further evidence supporting causal relationships between inflammation and tumor growth, and demonstrate that bortezomib can target the tumor microenvironment.

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Acknowledgements

This work was supported in part by a Japanese Grant-in-Aid for Scientific Research, (C) 20591118. We thank Dr Akio Masuda for helpful suggestions. We also wish to express our appreciation to Ms Chika Wakamatsu for her technical assistance.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    H Mizuno, T Nakayama, Y Miyata, S Saito, S Nishiwaki, N Nakao & T Naoe

  2. Department of Cardiology, Nagoya University Hospital, Nagoya, Japan

    K Takeshita

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  1. H Mizuno
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Correspondence to T Nakayama.

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Mizuno, H., Nakayama, T., Miyata, Y. et al. Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib. Leukemia 26, 2269–2276 (2012). https://doi.org/10.1038/leu.2012.81

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