Poletajew Sławomir, Fus Lukasz, Wasiutyński Aleksander
Department of Pathology, Medical University of Warsaw, Warsaw, Poland.
Ortop Traumatol Rehabil. 2011 Nov-Dec;13(6):537-45. doi: 10.5604/15093492.971038.
Osteosarcoma (OS) remains the most common malignancy among orthopaedic neoplasms. Despite advanced surgical techniques and attempts to use second-line chemotherapy, 5 year overall survival in OS patients is still reported to be as low as 60-70%. Progression to metastatic disease is the main cause of treatment failures. Broadening current knowledge on the pathogenesis and biology of metastatic OS tumors is a key element in improving treatment results, i.e. identifying potential therapeutic targets. Recent studies have brought new concepts into this field. This paper outlines the most important issues which may influence treatment methods in the near future. In a few sections, we discuss (1) a model of OS dissemination with special regard to proteins mediating the lysis of the extracellular matrix; (2) the mechanisms protecting circulating OS cells from programmed death; (3) the relationship between angiogenesis, its pathogenesis, and OS metastatic potential; (4) the role of cytokines in OS progression and site-specific metastasis formation; (5) an example of treatment resistance mechanism - the P glycoprotein efflux pump; and, finally, we theorize on (6) whether cancer stem cells may play a role in OS progression.
骨肉瘤（OS）仍然是骨科肿瘤中最常见的恶性肿瘤。尽管有先进的手术技术以及尝试使用二线化疗，但据报道，骨肉瘤患者的5年总生存率仍低至60%-70%。进展为转移性疾病是治疗失败的主要原因。拓宽当前对转移性骨肉瘤肿瘤发病机制和生物学的认识是改善治疗效果的关键因素，即确定潜在的治疗靶点。最近的研究为该领域带来了新的概念。本文概述了可能在不久的将来影响治疗方法的最重要问题。在几个部分中，我们讨论：（1）骨肉瘤播散模型，特别关注介导细胞外基质裂解的蛋白质；（2）保护循环中的骨肉瘤细胞免于程序性死亡的机制；（3）血管生成、其发病机制与骨肉瘤转移潜能之间的关系；（4）细胞因子在骨肉瘤进展和特定部位转移形成中的作用；（5）治疗耐药机制的一个例子——P糖蛋白外排泵；最后，我们推测（6）癌症干细胞是否可能在骨肉瘤进展中发挥作用。
