Clinical Cancer esearch cer Therapy : Preclinical rleukin-27 Acts as Multifunctional Antitumor R nt in Multiple Myeloma

Download pose: Multiple myeloma (MM) derives from plasmablast/plasma cells that accumulate in the bone w. Different microenvironmental factors may promote metastatic dissemination especially to the on, causing bone destruction. The balance between osteoclast and osteoblast activity represents a l issue in bone remodeling. Thus, we investigated whether interluekin-27 (IL-27) may function as titumor agent by acting directly on MM cells and/or on osteoclasts/osteoblasts. erimental Design: The IL-27 direct antitumor activity on MM cells was investigated in terms of genesis, proliferation, apoptosis, and chemotaxis. The IL-27 activity on osteoclast/osteoblast differion and function was also tested. In vivo studies were done using severe combined immunodefinonobese diabetic mice injected with MM cell lines. Tumors from IL-27– and PBS-treated mice nalyzed by immunohistochemistry and PCR array. ults: We showed that IL-27 (a) strongly inhibited tumor growth of primary MM cells and MM cell hrough inhibition of angiogenesis, (b) inhibited osteoclast differentiation and activity and induced last proliferation, and (c) damped in vivo tumorigenicity of human MM cell lines through inhibif angiogenesis. clusions: These findings show that IL-27 may represent a novel therapeutic agent capable of Con inhibiting directly MM cell growth as well as osteoclast differentiation and activity. Clin Cancer Res;