[HTML][HTML] Interleukin-6 interweaves the bone marrow microenvironment, bone loss, and multiple myeloma

D Harmer, C Falank, MR Reagan - Frontiers in endocrinology, 2019 - frontiersin.org
D Harmer, C Falank, MR Reagan
Frontiers in endocrinology, 2019frontiersin.org
The immune system is strongly linked to the maintenance of healthy bone. Inflammatory
cytokines, specifically, are crucial to skeletal homeostasis and any dysregulation can result
in detrimental health complications. Interleukins, such as interleukin 6 (IL-6), act as
osteoclast differentiation modulators and as such, must be carefully monitored and
regulated. IL-6 encourages osteoclastogenesis when bound to progenitors and can cause
excessive osteoclastic activity and osteolysis when overly abundant. Numerous bone …
The immune system is strongly linked to the maintenance of healthy bone. Inflammatory cytokines, specifically, are crucial to skeletal homeostasis and any dysregulation can result in detrimental health complications. Interleukins, such as interleukin 6 (IL-6), act as osteoclast differentiation modulators and as such, must be carefully monitored and regulated. IL-6 encourages osteoclastogenesis when bound to progenitors and can cause excessive osteoclastic activity and osteolysis when overly abundant. Numerous bone diseases are tied to IL-6 overexpression, including rheumatoid arthritis, osteoporosis, and bone-metastatic cancers. In the latter, IL-6 can be released with growth factors into the bone marrow microenvironment (BMM) during osteolysis from bone matrix or from cancer cells and osteoblasts in an inflammatory response to cancer cells. Thus, IL-6 helps create an ideal microenvironment for oncogenesis and metastasis. Multiple myeloma (MM) is a blood cancer that homes to the BMM and is strongly tied to overexpression of IL-6 and bone loss. The roles of IL-6 in the progression of MM are discussed in this review, including roles in bone homing, cancer-associated bone loss, disease progression and drug resistance. MM disease progression often includes the development of drug-resistant clones, and patients commonly struggle with reoccurrence. As such, therapeutics that specifically target the microenvironment, rather than the cancer itself, are ideal and IL-6, and its myriad of downstream signaling partners, are model targets. Lastly, current and potential therapeutic interventions involving IL-6 and connected signaling molecules are discussed in this review.
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