Over-expression of the protein Dickkopf-1 (Dkk1) has been associated with multiple myeloma bone disease. Previous reports with the use of anti-Dkk1 neutralizing Ab directed strategies have demonstrated a pro-anabolic effect with associated anti-myeloma activity in 2 in vivo mouse models. However new insights on the role of the wnt pathway in osteoclasts (OC) are emerging and the potential effect of a neutralizing Ab to Dkk1 in osteoclastogenesis remains to be elucidated. In order to better define the effect of an anti-Dkk1 neutralizing Ab on osteoclastogenesis and myeloma , we studeied a novel anti-Dkk1 monoclonal Ab in our preclinical models. In vivo data confirmed the pro-anabolic and anti-MM effect. In vitro data in part confirmed the in vivo observation, suggesting an indirect anti-MM effect secondary to inhibition of osteoclastogenesis and thus the interaction between MM and bone microenvironment. However, when stuidies on osteoclastogenesis were extended to samples derived from MM patients, we observed a variable response to anti-Dkk1 treatment without correlation to expression of surface receptors for Dkk1 in OCs suggesting potential heterogeneity in the efficacy of such a strategy. In conclusion, Dkk1 is a promising target for the treatment of both MM and bone disease, and ongoing clinical studies will help elucidate its efficacy.
|Data di pubblicazione:||2013|
|Titolo:||In vivo and in vitro effects of a novel anti-Dkk1 neutralizing antibody in multiple myeloma|
|Autori:||Pozzi, Samantha; Fulciniti, Mariateresa; Yan, Hua; Vallet, Sonia; Eda, Homare; Patel, Kishan; Santo, Loredana; Cirstea, Diana; Hideshima, Teru; Schirtzinge, Linda; Kuhstoss, Stuart; Anderson, Kenneth C.; Munshi, Nikhil; Scadden, David; Kronenberg, Henry M.; Raje, Noopur|
|Digital Object Identifier (DOI):||10.1016/j.bone.2013.01.012|
|Appare nelle tipologie:||Articolo su rivista|
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