Lenalidomide inhibits lymphangiogenesis in preclinical models of mantle cell lymphoma

Kai Song, Brett H. Herzog, Minjia Sheng, Jianxin Fu, Michael McDaniel, Jia Ruan, Lijun Xia

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Lymphomas originate in and spread primarily along the lymphatic system. However, whether lymphatic vessels contribute to the growth and spreading of lymphomas is largely unclear. Mantle cell lymphoma (MCL) represents an aggressive non-Hodgkin's lymphoma. We found that MCL exhibited abundant intratumor lymphatic vessels. Our results demonstrated that the immunomodulatory drug lenalidomide potently inhibited the growth and dissemination of MCL in a xenograft MCL mouse model, at least in part, by inhibiting functional tumor lymphangiogenesis. Significant numbers of tumor-associated macrophages expressing vascular endothelial growth factor-C were found in both human MCL and mouse MCL xenograft samples. Lenalidomide treatment resulted in a significant reduction in the number of MCL-associated macrophages. In addition, in vivo depletion of monocytes/macrophages impaired functional tumor lymphangiogenesis and inhibited MCL growth and dissemination. Taken together, our results indicate that tumor lymphangiogenesis contributes to the progression of MCL and that lenalidomide is effective in decreasing MCL growth and metastasis most likely by inhibiting recruitment of MCL-associated macrophages.

Original languageEnglish
Pages (from-to)7254-7264
Number of pages11
JournalCancer research
Volume73
Issue number24
DOIs
StatePublished - Dec 15 2013

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