The Influence of Primary Microenvironment on Prostate Cancer Osteoblastic Bone Lesion Development

The loss of stromal TGF-beta signaling has been shown to initiate prostate cancer PCa and promote PCa progression. A further effect on osteoblastic bone lesion development was hypothesized and tested in this proposal. Using the ColcreTgfbr2 KO mice, we are able to knock out TGF-beta signaling specifically in the prostate fibroblasts and in bone osteoblasts. We found that PC3 cell osteolytic bone lesions were significantly increased in the KO mice tibiae compared to the flox mice tibia. bFGF was the only cytokine up-regulated among many others down-regulated in KOPC3 tibiae relative to FloxPC3 tibiae. However, osteoblastic bone lesions induced by LUCaP cells were inhibited in KO mice tibiae relative to Flox mice tibia in our preliminary study. Our findings suggest that osteoblastic TGF-beta signaling inhibits PCa osteolytic bone lesions but may promote PCa osteoblastic bone lesions.