Bertolini Giulia, Roato Ilaria
Tumor Genomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
C.I.R. Dental School, Department of Surgical Sciences, Bone and Dental Bioengineering Laboratory, University of Turin, 10126 Turin, Italy.
Bone Rep. 2022 Sep 5;17:101619. doi: 10.1016/j.bonr.2022.101619. eCollection 2022 Dec.
Despite advancement in therapeutic options, Non-Small Cell lung cancer (NSCLC) remains a lethal disease mostly due to late diagnosis at metastatic phase and drug resistance. Bone is one of the more frequent sites for NSCLC metastatization. A defined subset of cancer stem cells (CSCs) that possess motile properties, mesenchymal features and tumor initiation potential are defined as metastasis initiating cells (MICs). A better understanding of the mechanisms supporting MIC dissemination and interaction with bone microenvironment is fundamental to design novel rational therapeutic option for long lasting efficient treatment of NSCLC. In this review we will summarize findings about bone metastatic process initiated by NSCLC MICs. We will review how MICs can reach bone and interact with its microenvironment that supports their extravasation, seeding, dormancy/proliferation. The role of different cell types inside the bone metastatic niche, such as endothelial cells, bone cells, hematopoietic stem cells and immune cells will be discussed in regards of their impact in dictating the success of metastasis establishment by MICs. Finally, novel therapeutic options to target NSCLC MIC-induced bone metastases, increasing the survival of patients, will be presented.
尽管治疗方案有所进展，但非小细胞肺癌（NSCLC）仍然是一种致命疾病，主要原因是在转移阶段诊断较晚以及耐药性。骨骼是NSCLC转移较常见的部位之一。具有运动特性、间充质特征和肿瘤起始潜能的特定癌症干细胞（CSC）亚群被定义为转移起始细胞（MIC）。更好地理解支持MIC传播以及与骨微环境相互作用的机制，对于设计新型合理治疗方案以长期有效治疗NSCLC至关重要。在本综述中，我们将总结关于NSCLC MIC引发的骨转移过程的研究结果。我们将回顾MIC如何到达骨骼并与其微环境相互作用，这种微环境支持它们的外渗、播种、休眠/增殖。骨转移龛内不同细胞类型（如内皮细胞、骨细胞、造血干细胞和免疫细胞）的作用将根据它们对MIC建立转移成功与否的影响进行讨论。最后，将介绍针对NSCLC MIC诱导的骨转移的新型治疗方案，以提高患者的生存率。
