Fusion between cervical cancer cells, HeLa cells, led to vast cell death, even though parental cells had low levels of p53. In the process, the fused cells showed mitotic defect such as formation of spindle multipolarity due to increased centrosomes, resulting in asymmetric division. In addition, when the fate of daughter cells was traced, multinucleated cells showed tendency to die. However, surviving fused cells, were characterized by upregulation of survivin, reflecting increased survivin protein stability. Moreover, in fused cells, survivin became preferentially localized to the cytosol, where it is known to exert its anti-apoptotic function. Knockdown of survivin decreased survival to a greater extent in fused cells than in unfused cells, suggesting that fused cells became more dependent on survivin. Therefore, above findings indicate that, after cancer cell fusion, a subpopulation of fused cells with a higher level of cytosolic survivin are able to avoid apoptotic crisis and survive to proliferate continuously, a process that might contribute to human cancer progression. Fused cells occuring depolyploidization had similar amounts of DNA and proliferated but showed genetic instability, which is far superior to cell migration or chemoresistance, which could have detrimental effects on cancer therapy. This suggests that fused cells made from isotypic parental cells may lead to more severe tumor heterogeneity, a difficult problem in cancer treatment, and that cell fusion may result in genome diversity.
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증식을 보이는 세포주에서도 염색체 불안정성이 유도된 것을 알 수 있었다. 특히, 세포사멸에서 살아남은 세포군은 안정적으로 증식을 한다는 것이다. 융합된 세포군 에서 항 세포사멸 기능을 갖는 survivin 단백질의 안정성 증가와 세포질에 존재하는
survivin의 증가를 알 수 있었다. survivin의 결핍은 비 융합세포와 비교 시 융합 된 세포의 생존율 감소를 초래하는 것으로 보아 survivin에 더 의존적임을 알 수 있었 다. 따라서 위의 결과는 암세포간의 융합 후에 세포질에 존재하는 survivin이 더 높 은 수준으로 증가한 융합 세포군이 세포사멸의 위기를 피하여 지속적으로 증식하므 로 암 진행에 기여할 수 있음을 시사한다. 암 진행과 관련하여 융합 세포는 비 융 합 세포보다 전체적인 세포 이동 능력이 뛰어 났으며 각 세포주에 따라 세포 이동 능이 다양하게 나타났다. 또한, 저농도의 cisplatin을 가한 경우, 융합 세포는 융합되 지 않은 세포보다 저항성이 높았다. 암세포의 융합은 p53 의존성 세포 사멸을 유도 하는 염색체 불안정성을 초래한다. 그러나 암세포간의 융합에서 세포질 내 survivin 이 더 증가된 세포군이 생존에 유리하고 유전적 다양성을 갖는 것을 알 수 있었고 이러한 유전적 다양성이 아마도 항암치료의 저항성 및 이동 능력의 획득과 같은 더 진보된 특성을 갖게 함을 알 수 있었다.
세포 융합, 세포 사멸, survivin, 비대칭적 분열, 유전체 불안정성