The Bone Microenvironmental Effect in the Dormancy of Cancer

Abstract

Tumors have already threatened human life and health for centuries, especially the recurrent of bone metastases is difficult to cure. Relapse can occur years to decades after resection of primary tumor. This phenomenon is common in many clinical cases and animal experimental studies. The effect of traditional radiotherapy and chemotherapy on relapse is very limited, and the patients' prognosis is poor. Because the delayed occurrence of metastases, researchers put forward a new concept "dormancy", including a single dormant tumor cell (growth-arrest) and tumor mass dormancy (equivalence of the proliferation rate and apoptosis rate). It is probable that dormant tumor cells are the resource of relapse and the main reason of chemotherapy resistance. The mechanisms mediated tumor cell dormancy are complex and poorly understood, and bone marrow microenvironment plays an important role in this process. This review focuses on the bone marrow microenvironmental effect in inducing cancer cells to dormancy uncovered by the latest researches.

The Autophagic Process Occurs in Human Bone Metastasis and Implicates Molecular Mechanisms Differently Affected by Rab5a in the Early and Late Stages

“…Numerous stimuli that trigger autophagy might be present in bone metastatic tissue ( Figure 5 C): autophagy is up-regulated when the cells need to generate intracellular nutrients and energy. It is known that bursts of oxygen radicals are activated downstream of growth factor/receptors couples in the bone marrow, a dynamic microenvironment of metastasis [ 15 , 28 , 29 ], and defective tumour mitochondria might release oxygen radicals [ 30 , 31 ]. Areas of hypoxia are known to occur also in bone metastasis [ 32 ].…”