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IONIZING RADIATION-INDUCED CANCER STEMNESS GENE EXPRESSI ON IS REGULATED BY MATRI X NANOTOPOGRAPHY

奈米表面結構可調控游離輻射所誘導的癌幹細胞基因表現

摘要


Introduction: Recent studies have revealed that nanoscale structure (nanotopography) of extracellular matrix is an important regulator of cell biology. However, it remains unknown whether nanotopography regulates cancer cell behaviors upon exposure to ionizing radiation (IR). Materials and Methods: Hepatoma cell lines and a squamous cell carcinoma cell line were cultured on nanopatterned polycaprolactone surfaces and were irradiated. Sphere formation was counted and expression of cancer stemness-related genes (Sox2, Nanog and Oct3/4) was measured with quantitative polymerase chain reaction. Results: In this study, we showed that IR induced expression of stemness genes including Sox2, Nanog and Oct3/4 in several cancer cell lines. Growing J5 hepatoma cells on a square lattice of evenly-spaced nanopits made of polycaprolactone attenuates cancer stemness genes expression induced by IR. Growing J5 cells on a near-square lattice of nanopits has smaller effects on IR-induced cancer stemness genes expression. The phenomenon was reproducible in another cell line derived from squamous cell carcinoma. Conclusions: We provided experimental evidence that radiation-induced expression of cancer stemness genes in cancer cells is regulated by nanotopography of the attaching surface. Further research is warranted to analyze molecular interaction between integrin signaling and cancer stemness, as well as the implications for cancer radiotherapy.

並列摘要


前言:近年研究發現細胞外間質與細胞接觸面的奈米表面結構是影響細胞生物學的重要特性,但是此類結構因素是否影響癌細胞對游離輻射的反應仍屬未知。材料與方法:本研究讓肝癌或鱗狀上皮癌細胞貼附在具特定奈米結構的聚己內酯表面,在顯微鏡下觀察球體形成,並利用定量聚合酶連鎖反應測量游離輻射誘導癌細胞癌幹細胞特性基因(Sox2, Nanog, Oct3/4)的表現。結果:研究結果發現游離輻射可誘導肝癌表現癌幹細胞特性基因。若將肝癌細胞株J5種植在均勻分散奈米孔表面,則此現象明顯被抑制。若將肝癌細胞株J5種植在奈米尺度近均勻分散奈米孔表面,則游離輻射仍可誘導肝癌細胞表現癌幹細胞特性基因。奈米結構對游離輻射誘導癌幹細胞特性基因表現的影響,亦在另一鱗狀上皮癌細胞株獲得證實。結論:本研究提供實驗證據,顯示游離輻射誘導癌幹細胞特性基因表現的過程受細胞貼附表面的奈米結構所調控。Integrin訊息傳遞與癌幹細胞特性基因表現之間的分子互動機制,以及在放射腫瘤生物學的應用值得後續探討。

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