Eriko Nakagomi1,2, Tetuo Mikami3, Kimihiko Funahashi4, Shinichi Okazumi5, Kazutoshi Shibuya6, Nobuyuki Hiruta7, Yoshinori Igarashi2,8. 1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Graduate School of Medicine, Ota-ku, Tokyo, Japan. eriko.nakagomi@med.toho-u.ac.jp. 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center Omori Hospital, Ota-ku, Tokyo, Japan. 3. Department of Pathology, Faculty of Medicine, Toho University, Tokyo, Japan. 4. Division of General and Gastroenterological Surgery, Department of Surgery, Toho University Medical Center Omori Hospital, Tokyo, Japan. 5. Department of Surgery, Toho University Medical Center Sakura Hospital, Sakura, Japan. 6. Department of Surgical Pathology, Toho University Medical Center Omori Hospital, Tokyo, Japan. 7. Department of Surgical Pathology, Toho University Medical Center Sakura Hospital, Sakura, Japan. 8. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Graduate School of Medicine, Ota-ku, Tokyo, Japan.
Abstract
OBJECTIVE: To elucidate tumor cell behavior associated with cancer stem cell (CSC) marker expression, the expression of CD133, CD44v9, and ALDH1A1, which are considered markers of CSCs, was examined in sporadic and ulcerative colitis (UC)-associated colorectal tumors. METHODS: A total of 23 cases of sporadic colorectal cancer and 44 cases of adenoma were collected. Additionally, 22 cancer lesions and 38 dysplasia lesions were selected from 28 colectomy cases of UC with neoplastic lesions. Lesions were examined by immunohistochemistry using primary antibodies against CD133, CD44v9, ALDH1A1, Ki-67, cleaved-Caspase 3, and p53. RESULTS: CD133, CD44v9, and ALDH1A1 showed higher expression in both sporadic and UC-associated tumors than in the normal mucosa. ALDH1A1 expression in sporadic cancer was higher in the right colon than in the left colon (p=0.0089). ALDH1A1 expression in UC-associated cancer was higher in those with longer disease duration than in those with shorter disease duration (p=0.019). The CD44v9+/CD133- region had fewer cleaved-Caspase 3 positive cells in both sporadic and UC-associated cancers. In sporadic cancer, CD133+/ALDH1A1+ regions had fewer apoptotic cells than CD133+/ALDH1A1- regions, while CD133+/ALDH1A1- regions were less proliferative than CD133+/ALDH1A1+ regions in UC-associated cancer. CONCLUSION: CD44+/CD133- regions were commonly associated with low apoptosis in sporadic and UC-associated cancers; thus, these were considered target areas for CSCs. Additionally, the combination of markers comprising CSCs may differ between sporadic and UC-associated cancers.
OBJECTIVE: To elucidate tumor cell behavior associated with cancer stem cell (CSC) marker expression, the expression of CD133, CD44v9, and ALDH1A1, which are considered markers of CSCs, was examined in sporadic and ulcerative colitis (UC)-associated colorectal tumors. METHODS: A total of 23 cases of sporadic colorectal cancer and 44 cases of adenoma were collected. Additionally, 22 cancer lesions and 38 dysplasia lesions were selected from 28 colectomy cases of UC with neoplastic lesions. Lesions were examined by immunohistochemistry using primary antibodies against CD133, CD44v9, ALDH1A1, Ki-67, cleaved-Caspase 3, and p53. RESULTS: CD133, CD44v9, and ALDH1A1 showed higher expression in both sporadic and UC-associated tumors than in the normal mucosa. ALDH1A1 expression in sporadic cancer was higher in the right colon than in the left colon (p=0.0089). ALDH1A1 expression in UC-associated cancer was higher in those with longer disease duration than in those with shorter disease duration (p=0.019). The CD44v9+/CD133- region had fewer cleaved-Caspase 3 positive cells in both sporadic and UC-associated cancers. In sporadic cancer, CD133+/ALDH1A1+ regions had fewer apoptotic cells than CD133+/ALDH1A1- regions, while CD133+/ALDH1A1- regions were less proliferative than CD133+/ALDH1A1+ regions in UC-associated cancer. CONCLUSION: CD44+/CD133- regions were commonly associated with low apoptosis in sporadic and UC-associated cancers; thus, these were considered target areas for CSCs. Additionally, the combination of markers comprising CSCs may differ between sporadic and UC-associated cancers.
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