TGFβ functions as a double-edged sword in prostate cancer tumourigenesis, in later stages promoting invasion and metastatic potential. One well-known cellular source of TGFβ-in the bone metastatic site is the bone-forming osteoblasts, contributing to disease progression through survival and growth of invading tumour cells. Here we have studied the effects by conditioned media from cultures of primary human osteoblasts on migration and metastatic potential in cells from the human bone metastatic prostate cancer cell line PC-3U. Osteoblast-conditioned media resulted in a morphological effect with an increase of long cellular protrusion of the PC-3U cells, an effect that appeared to be dependent on TGFβ-signalling. Also, migration was increased, an effect that was less prominent in PC-3U cells overexpressing a mutated TβRI receptor preventing TRAF6-dependent TGFβ-signalling. Furthermore, osteoblast-conditioned media increased invasive capacity of the PC-3U cells, but decreased proliferation. The effects of the osteoblast-derived factors on the PC-3U cells were not due to epithelial-mesenchymal transition (EMT) or neuroendocrine differentiation. The 3D Matrigel-on-top culture method was used for further evaluation of cell characteristics. Interestingly, treatment of PC-3U cells with osteoblast-conditioned media increased the formation of filopodia-like protrusions (FLPs), previously suggested to promote survival, migration and metastatic potential. In conclusion, the findings presented here suggests that factors secreted from osteoblasts, including TGFβ, can induce several cellular traits involved in metastatic potential of tumour cells, further strengthening the role by bone cells as inducers of metastatic tumour cell behaviour.
Disclosure: The authors declared no competing interests. This work was supported by AFA insurance (reference number 120338) and The Swedish Cancer Society (ref number CAN 2012/743).