Chalopin Antoine, Tellez-Gabriel Marta, Brown Hannah K, Vallette François, Heymann Marie-Françoise, Gouin Francois, Heymann Dominique
INSERM, U1238, Université de Nantes, Faculty of Medicine, rue Gaston Veil, Nantes, France.
Nantes University Hospital, CHU, Alexis Ricordeau, France.
J Bone Oncol. 2018 Jul 26;12:83-90. doi: 10.1016/j.jbo.2018.07.002. eCollection 2018 Sep.
Osteosarcoma is a rare primary bone tumor, which mainly affects children and adolescents and has a poor prognosis, especially for patients with metastatic disease. A poor therapeutic response to the conventional chemotherapy is observed with the development of lung metastases, highlighting the need for improving the current regimens and the identification of early markers of the recurrent and metastatic disease. Circulating Tumour Cells (CTCs) play a key role in the metastatic process and could be powerful biomarkers of the progressive disease. The present study aimed to isolate CTCs by using a pre-clinical model of human osteosarcoma and to monitor their kinetic of release and their modulation by ifosfamide. CTCs were detectable into the bloodstream before any palpable primary tumors. Ifosfamide increased CTCs count and in contrast decreased the number of lung tumor nodules. On established tumors, ifosfamide slowed down the tumour growth and did not modulate CTC count that could be explained by a release of cancer cells from the primary tumour with reduced properties for inducing lung metastases. This report highlights the biological interest of CTCs in osteosarcoma.
骨肉瘤是一种罕见的原发性骨肿瘤，主要影响儿童和青少年，预后较差，尤其是对于患有转移性疾病的患者。随着肺转移的发生，观察到对传统化疗的治疗反应不佳，这凸显了改进当前治疗方案以及识别复发和转移性疾病早期标志物的必要性。循环肿瘤细胞（CTCs）在转移过程中起关键作用，可能是疾病进展的有力生物标志物。本研究旨在通过使用人骨肉瘤临床前模型分离CTCs，并监测其释放动力学以及异环磷酰胺对其的调节作用。在任何可触及的原发性肿瘤出现之前，就能在血液中检测到CTCs。异环磷酰胺增加了CTCs计数，相反，减少了肺肿瘤结节的数量。在已形成的肿瘤上，异环磷酰胺减缓了肿瘤生长，但并未调节CTCs计数，这可能是由于原发性肿瘤释放出的癌细胞诱导肺转移的能力降低所致。本报告强调了CTCs在骨肉瘤中的生物学意义。
