BoneKEy Reports | BoneKEy Watch
Interaction between CD44 and hyaluronan promotes bone metastasis
CD44, the principal receptor for the extracellular matrix component hyaluronan (HA), is frequently overexpressed in cancer stem cells and has been implicated in the metastatic spread of various cancer types, including carcinomas, myeloma, and osteosarcoma. Hiraga et al. sought to understand more about the role of CD44 in bone metastasis by looking at the effect of reducing CD44 expression in cancer cell lines with a strong tendency to metastasize to bone.
Cells producing low levels of CD44 were less able to form tumor spheres in vitro. Formation of tumors in the orthotopic mammary fat pad of nude mice was inhibited when the mice were injected with tumor stem cells with a CD44 knockdown. Bone metastasis was similarly reduced and the metastases that did form contained significantly fewer osteoclasts.
Cells with reduced CD44 expression also expressed less HA synthase 2 and induced metastatic tumors in bone that showed reduced localization of HA. An inhibitor of HA synthesis as employed in vitro inhibited formation of monolayer cell proliferation and the formation of tumor spheres. When the inhibitor was used in bone marrow cultures, it suppressed the formation of osteoclast-like cells.
Editor’s comment: This study provides strong evidence that cancer cells expressing CD44 are more able to form bone metastases because of enhanced cell migration, invasion and tumorigenicity. Targeting the CD44–HA interaction could be an effective way to prevent the homing of cancer cells to bone.
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