Isolation and identification of human lung adenocarcinoma stem cells / 肿瘤

ABSTRACT

Objective: To isolate and characterize the highly tumorigenic cancer stem cells with stem cell features from the established human lung adenocarcinoma cell lines. Methods: The cell subtypes were separated by magnetic activated cell sorting (MACS) technique. The stem cell-related markers on the isolated cells were detected by using flow cytometry and RT-PCR. The tumorigenic potent of the isolated cells was evaluated via the transplantation into NOD-SCID mice. Results: A novel cell subtype was identified in A 549 and SPC-A1 lung adenocarcinoma cell lines. These cells were characterized as a phenotype of CD 24+ IGF-1R+, possessed the property of high invasiveness and high tumorigenesis. Tumor could be induced in NOD-SCID mice by transplantation of CD 24+IGF-1R+ cells at 100 cells per mouse. The tumorigenicity of CD 24+IGF-1R+ cells had 1000-fold increase compared with CD 24-IGF-1R- cells. In addition, the CD 24+IGF-1R+ cells expressed embryonic stem cell markers (OCT 4 and Bmi-1) and lung stem cell markers (CCSP, SP-C, TTF-1, and Gremlin), suggesting that they had the features identical to the bronchioalveolar stem cells (BASC) in the lung of mice. These cells also exhibited autonomous growth features and could be cultured in serum-free conditions for a long time. Conclusion: The CD 24+IGF-1R+ cells in human lung adeocarcinoma belongs to the BASC-like cancer stem cells.