| Title : Inhibitor of DASH proteases affects expression of adhesion molecules in osteoclasts and reduces myeloma growth and bone disease - Pennisi_2009_Br.J.Haematol_145_775 |
| Author(s) : Pennisi A , Li X , Ling W , Khan S , Gaddy D , Suva LJ , Barlogie B , Shaughnessy JD , Aziz N , Yaccoby S |
| Ref : Br J Haematol , 145 :775 , 2009 |
| Abstract : Dipeptidyl peptidase (DPP) IV activity and/or structure homologues (DASH) are serine proteases implicated in tumourigenesis. We previously found that a DASH protease, fibroblast activation protein (FAP), was involved in osteoclast-induced myeloma growth. Here we further demonstrated expression of various adhesion molecules in osteoclasts cultured alone or cocultured with myeloma cells, and tested the effects of DASH inhibitor, PT-100, on myeloma cell growth, bone disease, osteoclast differentiation and activity, and expression of adhesion molecules in osteoclasts. PT-100 had no direct effects on viability of myeloma cells or mature osteoclasts, but significantly reduced survival of myeloma cells cocultured with osteoclasts. Real-time PCR array for 85 adhesion molecules revealed upregulation of 17 genes in osteoclasts after coculture with myeloma cells. Treatment of myeloma/osteoclast cocultures with PT-100 significantly downregulated 18 of 85 tested genes in osteoclasts, some of which are known to play roles in tumourigenesis and osteoclastogenesis. PT-100 also inhibited osteoclast differentiation and subsequent pit formation. Resorption activity of mature osteoclasts and differentiation of osteoblasts were not affected by PT-100. In primary myelomatous severe combined immunodeficient (SCID)-hu mice PT-100 reduced osteoclast activity, bone resorption and tumour burden. These data demonstrated that DASH proteases are involved in myeloma bone disease and tumour growth. |
| ESTHER : Pennisi_2009_Br.J.Haematol_145_775 |
| PubMedSearch : Pennisi_2009_Br.J.Haematol_145_775 |
| PubMedID: 19388929 |
Pennisi A, Li X, Ling W, Khan S, Gaddy D, Suva LJ, Barlogie B, Shaughnessy JD, Aziz N, Yaccoby S (2009)
Inhibitor of DASH proteases affects expression of adhesion molecules in osteoclasts and reduces myeloma growth and bone disease
Br J Haematol
145 :775
Pennisi A, Li X, Ling W, Khan S, Gaddy D, Suva LJ, Barlogie B, Shaughnessy JD, Aziz N, Yaccoby S (2009)
Br J Haematol
145 :775