Analogy between sphere forming ability and stemness of human hepatoma cells

作者：Uchida Yusuke; Tanaka Shinji^*; Aihara Arihiro; Adikrisna Rama; Yoshitake Kenichirou; Matsumura Satoshi; Mitsunori Yusuke; Murakata Ayano; Noguchi Norio; Irie Takumi; Kudo Atsushi; Nakamura Noriaki; Lai Paul B; Arii Shigeki

来源：Oncology Reports, 2010, 24(5): 1147-1151.

DOI：10.3892/or_00000966

• sphere
• cancer stem cells
• p27
• p21
• chemoresistance
• hepatoma

Increasing evidence suggests that cancers contain a small subset of cancer-initiating cells, so-called cancer stern cells (CSCs) that are capable of regenerating a tumor after chemoradiation therapy. Sphere forming ability is known to be one of properties of CSCs, but the significance remains unclear. The present study focused on sphere formation of human hepatoma cells in three-dimensional culture in order to evaluate the analogy between sphere forming ability and sternness of cancer cells in vitro. Under three-dimensional culture condition, HepG2, Hep3B and PLC/PRF/5 cells demonstrated the sphere formation while SK-Hep1 and Huh-7 cells did not. The population of G0/G1 phase increased in the spheres compared with the monolayer (67 vs. 38%). In spite of no significant difference in stern cell surface markers (CD44, CD90, CD 133, EpCAM and ABCG2), remarkable up-regulation of p27 CDK inhibitor was observed in sphere forming cells. Immunofluorescence analysis revealed the nuclear expression of p27 in the whole of the sphere, but weak expression of p21 only at the peripheral area. The spheres acquired chemoresistance to cisplatin compared with the monolayers (58.9 vs. 16.2 mu M in IC50). This model was useful for assessment of the role of cell-cycle quiescence in the sternness and chemoresistance of cancer cells.

• 出版日期2010-11