| Popis: |
Multiple myeloma (MM) bone disease is a major contributor to the morbidity and mortality of MM patients due to pathological fractures. The MM cells interact with the cells of the bone microenvironment to both generate bone lesions as a result of enhanced induction of osteoclastogenesis and prevent reactive new bone formation to heal the lesions by repressing osteoblast activity. The MM stimulated osteoclasts (OCLs) not only generate bone lesions, but also interact with the myeloma cells to promote the proliferation and survival of the MM cells through the generation of interleukin-6 (IL-6), osteopontin, fibroblast activation protein, BAFF, APRIL, and annexin II. These MM-supportive OCL products present therapeutic opportunities. Further, the enhanced bone resorption by OCLs releases immobilized growth factors from the bone matrix that both support the MM cells and further stimulate OCL differentiation in a vicious cycle. Hence, targeting osteoclast activity may inhibit myeloma growth. Therefore, bisphosphonates have been investigated for their anti-tumor affects. The MM cells increase osteoclast activity both directly and by stimulation of microenvironmental production of RANKL, MIP-1α, TNF-α and interleukins IL-1b, IL-3 and IL-6. These are therefore also possible therapeutic targets to inhibit myeloma bone disease. |
