Targeted therapy against a particular protein has the potential to improve outcomes and fracture-free survival for patients with multiple myeloma, according to research that will be presented at the 2017 ASCO Annual Meeting (June 2-6, 2017; Chicago, IL).
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Myeloma bone disease is a product of osteoclast activation and long-term osteoblast suppression. Previous research has shown that Semaphorin 4D – the CD100 protein – is increased in the serum of patients with multiple myeloma and that co-culturing myeloma cell lines with osteocytes increases the expression of Semaphorin 4D mRNA. Semaphorin 4D has also shown activity in osteoblast inhibition as well as osteolysis in breast cancer cells.
Konstantinos Lontos, MD, department of medicine, University of Pittsburgh Medical Center (Pittsburgh, PA), and colleagues conducted a study to investigate the role of Semaphorin 4D in multiple myeloma cells to suppress bone formation and whether myeloma cells affect the levels of Semaphorin 4D produced by osteoclasts.
Researchers used lentivirus carrying shRNA for Semaphorin 4D or placebo to decrease the level of the protein in the 5TGM1 murine myeloma cell line. Subsequent co-cultured 5TGM1 cells with the MC3T3-subclone M4 (MC4) murine stromal cell line were undergone for 2 days, followed by removal of myeloma cells and differentiation of MC4 cells. After 5 days, the cells were analyzed for RUNx2 – a gene for the differentiation of stromal cells into osteoblasts – expression.
Researchers found that when 5TGM1 and placebo were co-cultured with MC4 cells, the expression of Runx2 after 5 days decreased significantly (P = .02). However, when 5TGM1 and Semaphorin 4D were co-cultured with MC4 cells, a different effect was observed and Runx2 expression was upregulated after 5 days (P = .01).
Results of the study suggest that multiple myeloma cells utilize Semaphorin 4D both directly and indirectly to inhibit bone formation, the authors wrote. Further research is needed to assess targeted therapies for Semaphorin 4D with the aim of improving outcomes and fracture-free survival for patients with this disease.—Zachary Bessette
