title: Lenalidomide inhibits lymphangiogenesis in preclinical models of mantle cell lymphoma.
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.
authors.affiliation: Authors' Affiliations: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Center for Lymphoma and Myeloma, Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York City, New York; China-Japan Union Hospital of Jilin University, Changchun; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health; and Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Song
authors.forename: Brett H
authors.initials: BH
authors.lastname: Herzog
authors.forename: Minjia
authors.initials: M
authors.lastname: Sheng
authors.forename: Jianxin
authors.initials: J
authors.lastname: Fu
authors.forename: J Michael
authors.initials: JM
authors.lastname: McDaniel
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Ruan
authors.forename: Lijun
authors.initials: L
authors.lastname: Xia
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D000077269:Lenalidomide; D042583:Lymphangiogenesis / Q000187:drug effects*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D011897:Random Allocation; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D000077269:Lenalidomide