Journal
LEUKEMIA
Volume 26, Issue 10, Pages 2269-2276Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2012.81
Keywords
Hodgkin's lymphoma; mast cells; angiogenesis; fibrosis; bortezomib
Categories
Funding
- [20591118]
- Grants-in-Aid for Scientific Research [22790907, 23591382] Funding Source: KAKEN
Ask authors/readers for more resources
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. Leukemia (2012) 26, 2269-2276; doi:10.1038/leu.2012.81
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available