Cancer stem cells in gastrointestinal carcinomas

In this review, we discuss recent issues concerning cancer stem cells, especially in the field of gastrointestinal carcinoma. Despite intensive therapy with anti-tumor agents or radiation, a portion of cancer cells survive, re-grow, and result in tumor recurrence. Such a cell population is thought to consist of cancer stem cells. Therefore, killing cancer stem cells is an eventual goal in conquering cancer. Recent studies have shown that cancer stem cells exist not only in leukemia, but also in gastrointestinal carcinomas such as colorectal cancer, pancreatic cancer, and hepatocellular carcinoma. Also in gastric cancer, cells like cancer stem cells are identified in the side population fraction. Several useful cell surface markers are proposed to collect organ-specific cancer stem cells. For example, CD133 ⁺, CD44 ⁺ or EpCAM ⁺ CD44 ⁺CD166 ⁺ for colorectal cancer, CD44 ⁺CD24 ⁺ESA ⁺, CD133 ⁺ for pancreatic cancer, and CD90 ⁺CD45 ^- for hepatocellular carcinoma may be promising markers. We evaluated the tumorigenicity of each population of human colon cancer cells divided by CD133 and CD44 using non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The combined analysis of CD133 and CD44 revealed that only the CD133 ⁺CD44 ⁺ population, but not CD133 ^-CD44 ^- and CD133 ⁺CD44 ^-, had the ability to produce a subcutaneous tumor (3/3), suggesting that the CD133 ⁺CD44 ⁺ population may be the best to identify tumor initiating cells of human colon cancer. Further comprehensive analysis on cancer stem cells is essential in terms of establishment a powerful and novel cancer therapy.