细胞融合和细胞间交互作用参与生理和病理过程以及肿瘤的发生和发展。前列腺癌最常见的转移部位是骨骼，骨转移是导致前列腺癌患者死亡的最主要原因之一。证据显示，肿瘤细胞产生的外分泌体与特定器官体细胞交互作用，促进肿瘤细胞器官特异性转移。我们和其他学者证实，前列腺癌发生初期，部分患者的骨髓中就可检测出肿瘤细胞，即所谓播散肿瘤细胞（DTCs），然而DTCs可以在骨髓中潜伏数年。我们在前期研究中发现肿瘤细胞与骨髓干细胞共培养后，部分肿瘤细胞与骨髓干细胞（HSCs）发生自发融合形成杂合细胞。我们的假设是骨微环境来源的外分泌体促进DTCs与HSCs融合，融合细胞具有肿瘤干细胞特性和转移的潜能。为此，本研究将采用GFP转基因小鼠的HSCs与鼠源前列腺癌细胞RM1或人前列腺癌细胞系PC3，C4-2B和VCaP细胞进行体外和体内融合，观察融合细胞的生物学性状改变。研究成果将阐明前列腺癌骨转移新的分子机制。

Both cell fusion and cell-cell communication participate multiple physiogical processes and pathological conditions including cancer development. Prostate cancer (PCa), for instance, preferentially metastasizes to skeleton that resulting in cancer-related high mortality. It has been shown that exosomes from mouse and human lung-, liver-, and bain-tropic tumor cells fused preferentially with resident cells at their predicted distant organs. Others and us have further demonstrated that at the early stage of PCa progression, disseminated tumor cells (DTCs) co-exist with bone microenvironment as dormancy/sleeping cells for years until being revoked by certain inducible conditions. However, how do these cells survive within this “hostile” environment and re-activate (wake-up) in the marrow when cancer relapse remain unknow. In our preliminary studies, our lab, for the first time, found that in vitro spontaneous fusion between murine PCa RM-1 cells and haematopoitic stem cells (HSCs). We thus hypothesize that exosomes derived from the bone microenvironment promotes the cell fusion; and the hybrids may gain the stem cell characteristics and metastatic potential within the pre-metastatic niche. In this study, we will used a GFP transgenic murine model to generate hybrids, in vivo, with human PC3, C4-2B, and VCap and murine RM1 cell lines and further to test whether the spontaneous cell fusion plays a key role in PCa metastastic process. Our results may suggest a novel mechanism for PCa skeletal metastasis and provide a molecular basis for identifing new therapeutic targets.