Selective Targeting of Cancer Stem Cells (CSCs) Based on Photodynamic Therapy (PDT) Penetration Depth Inhibits Colon Polyp Formation in Mice

Targeting cancer stem cells (CSCs) without damaging normal stem cells could contribute to the development of novel radical cancer therapies. Cells expressing leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) constitute a cancer-causing population in the colon; therefore, targeting of Lgr5+ cells is expected to provide an opportunity to mitigate colon cancer. However, the expression of Lgr5 in normal stem cells makes it difficult to prove the efficacy of therapies targeted exclusively at Lgr5+ cancer cells. We used a modified photodynamic therapy technique involving cellular radiative transfer between green fluorescent protein (GFP)-expressing cells and a rose bengal photosensitizer. After treatment, tumors containing GFP-Lgr5+ cells were observed to be significantly suppressed or retarded with little effect on GFP-Lgr5+ stem cells at the crypt bottom. Lgr5+ CSCs were specifically eradicated in situ, when localized based on the depth from the colon lumen, revealing the potential preventive efficacy of Lgr5-targeted therapy on tumor growth. This study supports the idea that Lgr5+ cells localized near the colon luminal surface are central to colorectal cancer. With further development, the targeting of localized Lgr5+ cancer stem cells, which this study demonstrates in concept, may be feasible for prevention of colon cancer in high-risk populations.