We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Anti-c- MET Nanobody<sup>®</sup> - a new potential drug in multiple myeloma treatment.
- Authors
Slørdahl, Tobias Schmidt; Denayer, Tinneke; Moen, Siv Helen; Standal, Therese; Børset, Magne; Ververken, Cedric; Rø, Torstein Baade
- Abstract
Background c- MET is the tyrosine kinase receptor of the hepatocyte growth factor ( HGF). HGF-c- MET signaling is involved in many human malignancies, including multiple myeloma ( MM). Recently, multiple agents have been developed directed to interfere at different levels in HGF-c- MET signaling pathway. Nanobodies® are therapeutic proteins based on the smallest functional fragments of heavy-chain-only antibodies. In this study, we wanted to determine the anticancer effect of a novel anti-c- MET Nanobody in MM. Methods We examined the effects of an anti-c- MET Nanobody on thymidine incorporation, migration, adhesion of MM cells, and osteoblastogenesis in vitro. Furthermore, we investigated the effects of the Nanobody on HGF-dependent c- MET signaling by Western blotting. Results We show that the anti-c- MET Nanobody effectively inhibited thymidine incorporation of ANBL-6 MM cells via inhibition of an HGF autocrine growth loop and thymidine incorporation in INA-6 MM cells induced by exogenous HGF. HGF-induced migration and adhesion of INA-6 were completely and specifically blocked by the Nanobody. Furthermore, the Nanobody abolished the inhibiting effect of HGF on bone morphogenetic protein-2-induced alkaline phosphatase activity and the mineralization of human mesenchymal stem cells. Finally, we show that the Nanobody reduced phosphorylation of tyrosine residues in c- MET, MAPK, and Akt. We also compared the Nanobody with anti-c- MET monoclonal antibodies and revealed the similar or better effect. Conclusions The anti-c- MET Nanobody inhibited MM cell migration, thymidine incorporation, and adhesion, and blocked the HGF-mediated inhibition of osteoblastogenesis. The anti-c- MET Nanobody might represent a novel therapeutic agent in the treatment of MM and other cancers driven by HGF-c- MET signaling.
- Subjects
PROTEIN-tyrosine kinases; HEPATOCYTE growth factor; CANCER; THYMIDINE; MESENCHYMAL stem cells
- Publication
European Journal of Haematology, 2013, Vol 91, Issue 5, p399
- ISSN
0902-4441
- Publication type
Article
- DOI
10.1111/ejh.12185