CD133(+) human pulmonary adenocarcinoma cells induce apoptosis of CD8(+) T cells by highly expressed galectin-3.

PURPOSE

To investigate the expression and function of Galectin-3 (Gal-3) in CD133(+) pulmonary adenocarcinoma.

METHODS

CD133(+) pulmonary adenocarcinoma cells were separated by MACS from excised pulmonary adenocarcinoma specimens of 11 patients. The percentage of CD133(+) cells in different cells population was determined by flow cytometry (FCM). Expression of Gal-3 in cancer cells was detected by Fluorescence Quantitation RT-PCR (FQRT-PCR) and Western blot whereas extracellular expression was detected by ELISA. CD133(+) cells were transfected with Gal-3 specific siRNA to explore the affects of Gal-3 inhibition on cancer cell growth and induction of CD8(+) T cell apoptosis.

RESULTS

Cells expressing CD133 constituted 90% of the CD133(+) subpopulation after separation by MACS whereas they made up only 1.2% of the unsorted cell population. Expression of Gal-3 was 1.24 fold, 1.5 fold and 2 fold higher in CD133(+) cells than in CD133(-) cells as detected by FQRT-PCR, Western blot and ELISA respectively (p < 0.05 for each). The supernatants of CD133(+) cells induced apoptosis of CD8(+) T cells to a greater degree (27.1+ or - 2.6%) compared with supernatants from CD133(-) cells (10.1 + or - 2.2%), and could be down-regulated by lactose, anti-galectin-3 polyclonal antibody and Gal-3 siRNA. Downregulation of Gal-3 resulted in significant inhibition of cancer cell growth in vitro.

CONCLUSION

Gal-3 is expressed at a relatively higher level in CD133(+) lung adenocarcinoma cells and could induce CD8(+) T cell apoptosis in vitro, both of which could be down-regulated by Gal-3 siRNA. These findings indicate that Gal-3 may play an important role during oncogenesis, implying a potential therapeutic target for pulmonary adenocarcinoma.