Lacunar-canalicular network in bone metastasis of prostate cancer as predisposing factor for weakness and fractures

One in 9 men will suffer from prostate cancer (PC) during his lifetime and 20% of them will face advanced metastatic disease. Bone metastases (BM) occur in ~80% of advanced PC patients causing severe pain and fractures that can generate spinal cord compression and immobility. Although PCBMs generate osteoblastic lesions with increased bone density, they still make bone weaker and easier to fracture. Our preliminary observations showed more and larger lacunae and altered canaliculi in PCBM, and lack of collagen organization. Here, we propose to use the X-ray phase-contrast nano-CT setup at the beam-line to analyze PCBM lacunar-canalicular network as a factor in understanding PCBM fragility. This beam-line, with the best available resolution and experience in 3D bone imaging, would help understanding lacunar-canalicular structure in PCBM, which can be related to stress accumulation and fractures, and provide insights on the intercellular communications in PCBM.

每9名男性在一生中都会罹患前列腺癌（prostate cancer, PC），其中20%的患者会进展为晚期转移性疾病。骨转移（bone metastases, BM）在约80%的晚期前列腺癌患者中发生，会引发剧烈疼痛与骨折，甚至可能导致脊髓压迫和肢体活动障碍。尽管前列腺癌骨转移（prostate cancer bone metastases, PCBM）会形成成骨性病变并提升骨密度，但仍会使骨骼强度降低，更易发生骨折。我们的初步观察显示，前列腺癌骨转移灶内存在更多、体积更大的骨陷窝（lacunae）与形态异常的骨小管（canaliculi），且胶原纤维缺乏有序排列。本研究拟依托光束线站的X射线相衬纳米计算机断层扫描（X-ray phase-contrast nano-CT）装置，对前列腺癌骨转移灶的骨陷窝-骨小管网络展开分析，以此为切入点解析前列腺癌骨转移灶的骨脆性机制。该光束线站拥有当前最优的成像分辨率及成熟的三维骨成像研究经验，将有助于阐明前列腺癌骨转移灶内骨陷窝-骨小管的结构特征——该结构与应力蓄积及骨折发生密切相关，同时也能为探究前列腺癌骨转移灶内的细胞间通讯机制提供新的研究视角。