Tumour cells produce receptor activator of NF-κB ligand (RANKL) in skeletal metastases
- L Huang1,
- Y Y Cheng1,
- L T C Chow2,
- M H Zheng3,
- S M Kumta4
- 1Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR
- 2Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong
- 3Department of Orthopaedic Surgery, University of Western Australia
- 4Department of Orthopaedics and Traumatology, Chinese University of Hong Kong; sm-kumta@cuhk.edu.hk
Osteolytic bone destruction is a common complication of tumours that metastasise to bone. Several solid tumours, most notably breast carcinoma, lung carcinoma, and prostate carcinoma, commonly metastasise to bone in patients with advanced disease, where they cause osteolysis and associated pain, hypercalcemia, and fracture. It is generally accepted that osteoclasts are the only cells capable of resorbing mineralised bone. In osteolytic metastases, it has been shown that tumour cells direct osteoclastic bone resorption through a vicious cycle1,2: in particular, tumour cell produced parathyroid hormone related protein (PTH-rP) facilitates bone resorption and, as a consequence, transforming growth factor β is released from the bone matrix and promotes the progression of bone metastases by further inducing PTH-rP production by tumour cells. Other tumour cell products, such as macrophage colony stimulating factor, interleukin 6 (IL-6), IL-11, and tumour necrosis factor α, have also been reported to be associated with tumour induced osteolysis.
However, with the identification and characterisation of a direct stimulator of osteoclastogenesis—the receptor activator of NF-kB ligand (RANKL,3,4 also …
