Biological significance of tumor budding at the invasive front of human colorectal carcinoma cells
At the invasive front of colorectal carcinoma (CRC), the existence of tumor budding (TB), the detachment and migration of small clusters of tumor cells from the neoplastic epithelium, correlates with high incidence of local invasion and distant metastasis; however, the molecular background of TB is still unknown. In human CRC-derived SW480 cells, CD133+ cells showed cancer stem cell (CSC)-like properties, high tumorigenicity and pluripotency. By a comparative study of gene expression between CD133+ and CD133- SW480 cells, high sensitivity against transforming growth factor-β (TGF-β) was suggested in CD133+ SW480 cells. Interestingly, treatment with recombinant TGF-β1 increased the numbers of cells expressing CD133 and SNAI1. Furthermore, in CD133- SW480 cells, the SNAI1-induced epithelial-mesenchymal transition (EMT) restored the population of CD133+ cells and increased tumorigenicity, cell motility/invasiveness and matrix metalloproteinase 2 (MMP2) expression. In stage II CRC tissues, TB was associated with increased levels of SNAI1 expression as well as high incidence of metachronous lymph node metastasis post-surgical resection. These findings suggest that TGF-β regulates not only the induction of EMT but also the restoration of CSCs in CRC. The tumor microenvironment at the invasive front is important for the formation of tumor buds in CRC.
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Document Type: Research Article
Affiliations: Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
Publication date: January 1, 2012
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- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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