The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo.

ABSTRACT: Multiple myeloma is a haematological malignancy that is dependent upon interactions within the bone microenvironment to drive tumour growth and osteolytic bone disease. Metformin is an anti-diabetic drug that has attracted attention due to its direct antitumor effects, including anti-myeloma properties. However, the impact of the bone microenvironment on the response to metformin in myeloma is unknown. We have employed in vitro and in vivo models to dissect out the direct effects of metformin in bone and the subsequent indirect myeloma response. We demonstrate how metformin treatment of preosteoblasts increases myeloma cell attachment. Metformin-treated preosteoblasts increased osteopontin (OPN) expression that upon silencing, reduced subsequent myeloma cell adherence. Proliferation marker

SUBMITTER: Gamez B 

PROVIDER: S-EPMC8665410 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature