Interleukin-27 acts as multifunctional antitumor agent in multiple myeloma.
OBJECTIVE
Multiple myeloma (MM) derives from plasmablast/plasma cells that accumulate in the bone marrow. Different microenvironmental factors may promote metastatic dissemination especially to the skeleton, causing bone destruction. The balance between osteoclast and osteoblast activity represents a critical issue in bone remodeling. Thus, we investigated whether interluekin-27 (IL-27) may function as an antitumor agent by acting directly on MM cells and/or on osteoclasts/osteoblasts.


METHODS
The IL-27 direct antitumor activity on MM cells was investigated in terms of angiogenesis, proliferation, apoptosis, and chemotaxis. The IL-27 activity on osteoclast/osteoblast differentiation and function was also tested. In vivo studies were done using severe combined immunodeficient/nonobese diabetic mice injected with MM cell lines. Tumors from IL-27- and PBS-treated mice were analyzed by immunohistochemistry and PCR array.


RESULTS
We showed that IL-27 (a) strongly inhibited tumor growth of primary MM cells and MM cell lines through inhibition of angiogenesis, (b) inhibited osteoclast differentiation and activity and induced osteoblast proliferation, and (c) damped in vivo tumorigenicity of human MM cell lines through inhibition of angiogenesis.


CONCLUSIONS
These findings show that IL-27 may represent a novel therapeutic agent capable of inhibiting directly MM cell growth as well as osteoclast differentiation and activity.
Cocco
Claudia
C
Department of Experimental and Laboratory Medicine, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Giuliani
Nicola
N
Di Carlo
Emma
E
Ognio
Emanuela
E
Storti
Paola
P
Abeltino
Manuela
M
Sorrentino
Carlo
C
Ponzoni
Maurilio
M
Ribatti
Domenico
D
Airoldi
Irma
I
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D016133:Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D007378:Interleukins; C464565:MYDGF protein, human