Role of Bone Remodeling in Skeletal Colonization by Prostate Cancer Cells

摘要

Prostate cancer metastasizes selectively to bone, but the role of host tissue in promoting skeletal metastasis is not fully understood. This project tests whether sites of bone remodeling (resorption and formation) are targets for initial tissue colonization by circulating prostate tumor cells. In this project human prostate cancer cell lines (LNCaP, PC3) expressing high levels of green fluorescent protein (GFP) were selected and found to have similar growth and adhesive properties to cells expressing lower GFP levels. Following injection into the vasculature of nude mice, both LNCaP and PC3 cells were identified in tibial metaphyses and found to localize preferentially to bone surfaces that are resorbing. This finding supports the hypothesis that initial colonization of bone by prostate cancer cells is at least partly targeted to areas of bone remodeling. In addition, inhibition of bone resorption by pre-treatment with a bisphosphonate inhibited colonization by LNCaP and PC3 cells, not only at resorbing sites but to a lesser extent near forming and quiescent bone. This suggests that bone resorption or remodeling may affect the ability of bone to support tumor cell colonization even at sites outside the immediate vicinity of bone turnover.