In prostate cancer TGFβ promotes invasion and metastatic potential. One well-known cellular source of TGFβ in the bone metastatic site is the bone-forming osteoblasts. Here we have studied the effects by human osteoblast-derived factors on metastatic potential in cells from the human bone metastatic prostate cancer cell line PC-3U and the primary prostate cancer cell line 22Rv1. Osteoblast-derived factors resulted in a morphological effect with an increase of long cellular protrusions of the PC-3U cells, an effect dependent on TGFβ-signaling. Also, migration was increased, an effect that was less prominent in PC-3U cells overexpressing a mutated TβRI receptor preventing TRAF6-dependent TGFβ-signaling. Furthermore, osteoblast-derived factors induced loss of cellcell contacts. The effects of the osteoblast-derived factors on the PC-3U cells were not due to epithelialmesenchymal transition or neuroendocrine differentiation. The 3D Matrigel-on-top culture method was used for further evaluation of cell characteristics. Interestingly, both 22Rv1 and PC-3U could generate filopodium-like protrusions (FLPs), protrusions previously suggested to be essential for breast cancer metastatis. FLP formation in 22Rv1 was rare, but ten times more frequent in PC-3U. Treatment of PC-3U cells with osteoblast-derived factors, or TGFβ alone, increased the formation of FLPs tenfold. In conclusion, the findings presented here suggest that factors secreted from osteoblasts, including TGFβ, can induce several cellular traits important in metastatic potential of tumor cells, further strengthening the role by bone cells as inducers of metastatic tumor cell behavior.
14 - 17 May 2016
European Calcified Tissue Society