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Full-Text Articles in Medicine and Health Sciences
Overexpression Of Matrix Metalloproteinase 9 In Tumor Epithelial Cells Correlates With Colorectal Cancer Metastasis., David S Zuzga, Ahmara Vivian Gibbons, Peng Li, Wilhelm Johannes Lubbe, Inna Chervoneva, Giovanni Mario Pitari
Overexpression Of Matrix Metalloproteinase 9 In Tumor Epithelial Cells Correlates With Colorectal Cancer Metastasis., David S Zuzga, Ahmara Vivian Gibbons, Peng Li, Wilhelm Johannes Lubbe, Inna Chervoneva, Giovanni Mario Pitari
Department of Pharmacology and Experimental Therapeutics Faculty Papers
Colorectal cancer mortality largely reflects metastasis, the spread of the disease to distant organs. Matrix metalloproteinase 9 (MMP-9) is a key regulator of metastasis and a target for anticancer strategies in colon cancer. Here, the overexpression of MMP-9 in pure tumor epithelial, but nor stromal, cell populations was associated with metastatic progression of colorectal cancer, as defined by reverse transcriptase-polymerase chain reaction (qRT-PCR) and confirmed by immunostaining. Thus, cancer cell MMP-9 represents a novel, selective prognostic and predictive factor that may be exploited for more effective disease stage stratification and therapeutic regimen selection in patients with colorectal cancer.
Enterotoxin Preconditioning Restores Calcium-Sensing Receptor-Mediated Cytostasis In Colon Cancer Cells, Giovanni Mario Pitari, Jieru E. Lin, Fawad J. Shah, Wilhelm J. Lubbe, David Zuzga, Peng Li, Stephanie Schulz, Scott A Waldman
Enterotoxin Preconditioning Restores Calcium-Sensing Receptor-Mediated Cytostasis In Colon Cancer Cells, Giovanni Mario Pitari, Jieru E. Lin, Fawad J. Shah, Wilhelm J. Lubbe, David Zuzga, Peng Li, Stephanie Schulz, Scott A Waldman
Department of Pharmacology and Experimental Therapeutics Faculty Papers
Guanylyl cyclase C (GCC), the receptor for diarrheagenic bacterial heat-stable enterotoxins (STs), inhibits colorectal cancer cell proliferation by co-opting Ca(2+) as the intracellular messenger. Similarly, extracellular Ca(2+) (Ca(2+)(o)) opposes proliferation and induces terminal differentiation in intestinal epithelial cells. In that context, human colon cancer cells develop a phenotype characterized by insensitivity to cytostasis imposed by Ca(2+)(o). Here, preconditioning with ST, mediated by GCC signaling through cyclic nucleotide-gated channels, restored Ca(2+)(o)-dependent cytostasis, reflecting posttranscriptional regulation of calcium-sensing receptors (CaRs). ST-induced GCC signaling deployed CaRs to the surface of human colon cancer cells, whereas elimination of GCC signaling in mice nearly abolished …