Tumor-host cell interactions in the bone disease of myeloma

Abstract

Multiple myeloma is a hematological malignancy that is associated with the development of a destructive osteolytic bone disease, which is a major cause of morbidity for patients with myeloma. Interactions between myeloma cells and cells of the bone marrow microenvironment promote both tumor growth and survival and bone destruction, and the osteolytic bone disease is now recognized as a contributing component to tumor progression. Since myeloma bone disease is associated with both an increase in osteoclastic bone resorption and a suppression of osteoblastic bone formation, research to date has largely focused upon the role of the osteoclast and osteoblast. However, it is now clear that other cell types within the bone marrow, including cells of the immune system, mesenchymal stem cells and bone marrow stromal cells, can contribute to the development of myeloma bone disease. This review discusses the cellular mechanisms and potential therapeutic targets that have been implicated in myeloma bone disease.

Figure 1. Progression of our understanding of the complex cellular relationships in myeloma bone disease

(A) The original studies first described the relationship between myeloma cells and osteoclasts, whereby myeloma cells released “osteoclast activating factors' (OAFs) that stimulated osteoclastic bone resorption which in turn released growth factors which promoted myeloma cell growth and survival. (B) Our current knowledge has identified many more cell types and factors which contribute to disease progression, although the original concepts of tumor cells promoting bone destruction which in turn promote tumor growth remain the fundamental aspects of this increasingly complex network of interactions.