UCL Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, U.K.
Oncologist. 2010;15(6):627-35. doi: 10.1634/theoncologist.2010-0093. Epub 2010 May 17.
Detection of micrometastatic tumor cells in the bone marrow or peripheral blood of patients with Ewing family of tumors (EFTs) and osteosarcoma has been shown to correlate with poor outcome. Although one of the aims of chemotherapy is eradication of micrometastatic disease, these cells vary phenotypically from primary tumor cells and appear to be more resistant to chemotherapy. As a barrier to metastasis, cells normally undergo a form of cell death termed anoikis after they lose contact with the extracellular matrix or neighboring cells. Tumor cells that acquire malignant potential have developed mechanisms to resist anoikis and thereby survive after detachment from their primary site and while traveling through the circulation. Investigating mechanisms of resistance to anoikis, therefore, provides a valuable model to investigate regulation of micrometastatic disease. This review focuses on the current understanding of the mechanisms involved in mediating cell survival and resistance to anoikis in EFTs and osteosarcoma and discusses future studies that may help to identify novel therapeutics targeted at micrometastatic disease.
已经证实，检测尤文氏家族肿瘤（EFTs）和骨肉瘤患者骨髓或外周血中的微转移肿瘤细胞与不良预后相关。虽然化疗的目的之一是消除微转移疾病，但这些细胞在表型上与原发性肿瘤细胞不同，并且似乎对化疗更具抵抗力。作为转移的障碍，细胞在失去与细胞外基质或邻近细胞的接触后通常会经历一种称为失巢凋亡的细胞死亡形式。获得恶性潜能的肿瘤细胞已经开发出抵抗失巢凋亡的机制，从而在从原发性部位分离并在循环中移动时存活下来。因此，研究抵抗失巢凋亡的机制为研究调节微转移疾病提供了一个有价值的模型。这篇综述重点介绍了目前对介导 EFTs 和骨肉瘤中细胞存活和抵抗失巢凋亡的机制的理解，并讨论了未来可能有助于确定针对微转移疾病的新型治疗方法的研究。
