Supplementary Figures 1 - 11 from Lenalidomide Inhibits Lymphangiogenesis in Preclinical Models of Mantle Cell Lymphoma
PDF file - 4999K, Supplementary Figure S1. Characterization of lymphatic vessels in non-reactive lymph nodes and mantle cell lymphoma xenografts. Supplementary Figure S2. LEN treatment decreases MCL dissemination. Supplementary Figure S3. LEN treatment does not affect the function of pre-existing host collecting lymphatic vessels. Supplementary Figure S4. Disseminated MCL tumor cells are within the lymphatic vessels in the distant axillary lymph nodes. Supplementary Figure S5. LEN treatment does not affect the proliferation, survival, or migration of lymphatic endothelial cells in vitro. Supplementary Figure S6. Gene expression profiles of lymphatic endothelial cells, macrophages and MCL xenografts after LEN treatment. Supplementary Figure S7. LEN treatment decreases macrophages in tumor peripheral regions. Supplementary Figure S8. LEN treatment does not affect the proliferation, survival, migration or VEGF-C expression of macrophages in vitro. Supplementary Figure S9. Clodrolip treatment results in significant macrophage depletion at tumor peripheral regions. Supplementary Figure S10. Tumor lymphangiogenesis is affected at early stage after LEN treatment. Supplementary Figure S11. LEN treatment inhibits functional angiogenesis.
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ARTICLE 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. Cancer Res; 73(24); 7254–64. ©2013 AACR.Usage metrics
