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• W2188341453 abstract "Aim: To clarify the correlation between morphological features and the mRNA expression of a disintegrin and metalloproteinases (ADAMs) and matrix metalloproteinases (MMPs) in colorectal cancer. Materials and Methods: In 29 colorectal tumors, cancer cells were isolated by laser microdissection, and the mRNA expression of metalloproteinases was compared between the tumor center and the invasive front. Results: Regarding the central region as the standard, the mRNA levels of ADAM-12, MMP- 1, -2, -7, and -9 at the invasive front were up-regulated. The degree of up-regulation was significantly higher in solid cancer nest (SCN)-positive tumors than in SCN-negative tumors for the mRNA levels of ADAM-12, MMP-2, -7, and - 9 (SCN-positive, median 5.1-, 3.9-, 9.9-, and 2.7-fold; SCN- negative 2.0-, 1.0-, 2.4-, and 0.8-fold; p<0.05, respectively). Conclusion: Up-regulation of the mRNA expression of particular metalloproteinases was significantly associated with the SCN at the leading edge of colorectal tumors. The biological activity of colorectal cancer is thought to be more accurately reflected by histological characteristics (such as tumor budding) at the invasive front than in the central area of the tumor (1-3). We have previously shown that the extent of the cancerous area without a gland structure in the invasive front of colorectal cancer is an independent prognosticator, namely that advanced colorectal tumors having few solid cancer nests with no glandular formation (SCN) are associated with a very favorable prognosis. (4) However, the molecular biological characteristics of this heterogeneous morphological feature exclusively observed at the invasive front have remained unclear. Two metalloproteinase families, matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs), which are regulated by tissue inhibitors of metalloproteinases (TIMPs), have been shown to correlate with tumor invasion. MMPs appear to play an important role in cancer cell proliferation and progression through the process of degradation of the extracellular matrix, processing of growth factors, and activation of cell adhesion molecules (5, 6). ADAMs are members of an MMP-related metalloproteinase family, and are kinds of type I transmembrane proteins that contain a metalloprotease and a disintegrin-like domain (7). Recent reports have shown that by cleaving different components, ADAMs direct cell migration and control various signaling pathways activated in cancer cells. Some ADAM species, including ADAM-10, -12, and -17, are known to be expressed in human colorectal cancer, although the details of their role in the progression of colorectal cancer have not been clarified (7, 8). The aim of this study was to identify the molecular biological characteristics of this heterogeneous morphological feature at the invasive front of colorectal tumors. First, we examined the pathological significance of the difference in tumor expression of mRNA of ADAMs, MMPs, and TIMPs, between the center of tumor and the invasive front, using laser microdissection and a real-time RT-PCR method. We then analyzed the RNA expression status of these molecules, with special reference to the formation of SCNs at the leading edge of the tumor." @default.
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• W2188341453 date "2011-05-01" @default.
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• W2188341453 title "Heterogeneity of metalloproteinase expression in colorectal cancer - relation of molecular findings to basic morphology." @default.
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