Canine osteosarcoma cells exhibit basal accumulation of multiple chaperone proteins and are sensitive to small molecule inhibitors of GRP78 and heat shock protein function

• DOI: 10.1007/s12192-022-01263-3
• Publication Date: 2022-03-04T15:34:48Z
• Authors: Daphne R. Mattos; Marcus A. Weinman; Xuemei Wan; Cheri P. Goodall; Jeffrey D. Serrill; Kerry L. McPhail; Milan Milovancev; Shay Bracha; Jane E. Ishmael
• Keywords: Carboplatin; Proteome; Chaperone (clinical)

Osteosarcoma is the most common type of bone cancer in dogs and humans, with significant numbers patients experiencing treatment failure disease progression. In our search for new approaches to treat osteosarcoma, we previously detected multiple chaperone proteins surface-exposed proteome canine osteosarcoma cells. present study, characterized expression representative chaperones find evidence stress adaptation cells relative osteogenic progenitors from normal bone. We compared cytotoxic potential direct (HA15) putative (OSU-03012) inhibitors Grp78 function found POS HMPOS be more sensitive both compounds than HA15 OSU-03012 increased thermal stability intact at low micromolar concentrations, but each induced distinct patterns without change Grp94. Both were as effective alone carboplatin showed little synergy combination treatment. However, acquired resistance inhibition (by HA15; OSU-03012), Hsp70 VER-155008), Hsp90 17-AAG) function. These results suggest that nodes within chaperome may relevant chemotherapeutic targets against platinum resistance.