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

H. Mizuno, T. Nakayama, Y. Miyata, S. Saito, S. Nishiwaki, N. Nakao, K. Takeshita, T. Naoe

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2269-2276
Number of pages8
JournalLeukemia
Volume26
Issue number10
DOIs
Publication statusPublished - 10-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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