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

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.