PMID: 25755907Jan 1, 2014Paper

Dkk-1 and IL-7 in plasma of patients with multiple myeloma prevent differentiation of mesenchymal stem cells into osteoblasts

American Journal of Blood Research
Brittany A NiersteJulia Kirshner

Abstract

Bone disease is the leading cause of morbidity associated with multiple myeloma (MM). Lytic bone lesions have been detected in 90% of patients diagnosed with MM and present a great therapeutic challenge. After the removal of the tumor burden, the bone lesions persist and the bone remodeling homeostasis is not restored even in patients in clinical remission. To determine whether systemic factors generated by malignant MM cells can skew the osteoblast (OB) differentiation program of normal mesenchymal stem cells (MSCs), we generated an immortalized bone marrow MSC line (hTERT-MSC). The hTERT-MSCs were exposed to plasma from healthy donors and patients with MM. Cells grown in media supplemented with plasma from MM patients failed to differentiate into OBs, while the hTERT-MSCs grown in the presence of normal human plasma generated OB clusters that mineralized calcium, expressed Runx2, and were positive for alkaline phosphatase, fibronectin, collagen I, osteocalcin, and osteopontin. Blocking Dickkopf-1 (Dkk-1) and interleukin-7 (IL-7) in MM plasma restored proper OB differentiation of hTERT-MSCs. Finally, we show that hTERT-MSCs cultured in the presence of MM plasma adopt a cancer-associated stroma phenotype. Thus, we show, that sy...Continue Reading

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