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Elevated expression of angiomodulin (AGM/IGFBP-rP1) in tumor stroma and its roles in fibroblast activation

  1. Top of page
  2. Elevated expression of angiomodulin (AGM/IGFBP-rP1) in tumor stroma and its roles in fibroblast activation
  3. Dickkopf-1 inhibits epithelial–mesenchymal transition of colon cancer cells and contributes to colon cancer suppression
  4. Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma
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Page 691–99

Angiomodulin (AGM), a glycoprotein originally identified as a tumor-derived cell adhesion factor, has been reported as contributing to tumor progression and suppression. Some studies report that AGM is overexpressed in tumor vasculature and in some human cancer cell lines, however, others show that reduced expression of AGM is associated with worse prognosis in breast, prostate, and lung cancers. In their work towards elucidating the role of AGM in tumor progression, Komiya and colleagues investigated the expression and distribution of AGM in human cancer tissues of the lung, colon, and uterus. Immunohistochemistry analysis revealed overexpression of AGM in the stromal fibroblasts and vasculature of all three cancers. In vitro analysis of the biological activity of AGM suggested that AGM activates normal fibroblasts by transforming growth factor (TGF)-β-dependent and independent mechanisms. Results suggest that AGM and TGF-β1 may cooperatively or complementarily contribute to stromal activation and connective tissue formation in cancer tissues.

Dickkopf-1 inhibits epithelial–mesenchymal transition of colon cancer cells and contributes to colon cancer suppression

  1. Top of page
  2. Elevated expression of angiomodulin (AGM/IGFBP-rP1) in tumor stroma and its roles in fibroblast activation
  3. Dickkopf-1 inhibits epithelial–mesenchymal transition of colon cancer cells and contributes to colon cancer suppression
  4. Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma
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Page 828–35

The Wnt/β-catenin pathway drives proliferation and dedifferentiation in 90% of colorectal cancers. There is some evidence that Wnt/β-catenin signaling contributes to epithelial–mesenchymal transition (EMT), a critical step in tumor progression. Dickkopf-1 (Dkk1) is a potent inhibitor of Wnt signaling that may be induced by Wnt as part of a negative feedback loop in normal tissues. This autoregulatory mechanism of Dkk1 might be lost in colorectal cancer. In this issue, Qi and colleagues provide evidence that Dkk1 inhibits EMT in colon cancer. The researchers found an inverse correlation between Dkk1 and tumor stage and the presence of metastatsis and recurrence in 217 colon cancer tissue samples. Overexpression of Dkk1 reduced proliferation, migration, and invasion of colon cancer cells. In a nude mouse xenograft model, upregulation of Dkk1 led to decreased tumor-initiating ability and suppressed colon tumor growth. The results indicate that Dkk1 can suppress colon cancer progression and may have potential for anticancer therapy.

Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma

  1. Top of page
  2. Elevated expression of angiomodulin (AGM/IGFBP-rP1) in tumor stroma and its roles in fibroblast activation
  3. Dickkopf-1 inhibits epithelial–mesenchymal transition of colon cancer cells and contributes to colon cancer suppression
  4. Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma
Thumbnail image of

Page 739–46

Pancreatic ductal adenocarcinoma (PDAC) has the propensity for early local invasion and vascular dissemination, leading to a poor prognosis for patients, most of whom are diagnosed at an advanced stage. Shimizu and colleagues sought to identify genes involved in the invasion process of PDAC. The researchers compared microarray data of infiltrating cancer and a precursor lesion called pancreatic intraepithelial neoplasm-3 (PanIN-3) from an individual patient with PDAC. Eighty-seven genes were upregulated in infiltrating components as compared to PanIN-3. Further analysis focused on MUC16, the most upregulated gene, and mesothelin, a MUC16 ligand. MUC16 and mesothelin were expressed simultaneously only in infiltrating components, and this coexpression was greater at the invasion front. Both downregulating MUC16 and blocking MUC16–mesothelin binding inhibited invasion and migration. The results suggest that MUC16 and mesothelin are involved in pancreatic cancer cell invasion and migration and could represent new prognostic biomarkers for PDAC and novel therapeutic targets.