The effect of the characteristic desmoplastic reaction of pancreatic cancer on tumor progression is largely unknown. We investigated whether pancreatic stellate cells, which are responsible for the desmoplastic reaction, support tumor progression. Immunohistology revealed that

Objective-Matrix metalloproteinases (MMPs) seem to play a prominent role in atherogenesis. Extracellular MMP inducer (EMMPRIN), a cell surface glycoprotein which stimulates MMP synthesis, has recently been detected in human atheroma. We have investigated the influence of oxidized low-density lipoproteins (oxLDLs) on EMMPRIN expression in human coronary artery smooth muscle cells (HCA-SMCs). Methods and Results-OxLDL induced a significant increase of EMMPRIN release into HCA-SMC supernatants and a concomitant decrease of cell-associated EMMPRIN. These effects were antagonized by antioxidants as well as by EDTA and the MMP inhibitor GM6001. Western blot analysis demonstrated that MMP-1 and MMP-2 induce the cleavage of the extracellular domain from cell-associated EMMPRIN. MMP-1 and MMP-2 synthesis was upregulated by oxLDL, and, in addition, we have shown that soluble EMMPRIN, isolated from macrophage supernatants, increased MMP-1 and MMP-2 synthesis in HCA-SMC. Key Words: smooth muscle cells Ⅲ low density lipoproteins Ⅲ matrix metalloproteinases Ⅲ extracellular MMP inducer Ⅲ atherosclerosis D eposition of low-density lipoproteins (LDLs) in the vessel wall and their oxidative modification seem to initiate, or at least accelerate, the atherosclerotic process by several mechanisms, including promotion of foam cell formation, chemotactic effects on monocytes, and mitogenic effects on smooth muscle cells. Recent studies have demonstrated that oxidized LDLs (oxLDLs) increase the expression of matrix metalloproteinases (MMPs) in endothelial cells, monocyte-derived macrophages, and smooth muscle cells [1][2][3] and that MMP expression is enhanced in atherosclerotic plaque tissue. 4 MMPs increase smooth muscle cell migration and proliferation 5,6 and also seem to promote plaque instability by inducing extracellular matrix degradation. 7 Expression of extracellular MMP inducer (EMMPRIN) in human atheroma has been described recently. 8,9 EMMPRIN, also called CD147 or basigin, is a highly glycosylated plasma membrane protein (Ϸ58 kDa) belonging to the immunoglobulin superfamily. EMMPRIN is expressed on several cell types like leukocytes and different tumor cells 10 and stimulates MMP production in fibroblasts and various tumor cells. 11,12 Several studies have shown that cancer cells express significantly higher EMMPRIN levels than normal cells, and it has been proposed that elevated EMMPRIN expression in tumor cells may promote tumor progression by inducing MMP expression in peritumoral stromal cells. In this study, we have demonstrated that EMMPRIN is expressed in cultured human coronary artery smooth muscle cells (HCA-SMCs) and that oxLDL significantly enhanced the release of soluble EMMPRIN as well as MMP-1 and MMP-2 release. In addition, we have shown that MMP-1 and MMP-2 seem to promote the cleavage of soluble EMMPRIN from the cell surface and that soluble EMMPRIN stimulates MMP synthesis in HCA-SMC. Thus our data suggest that oxLDL might induce a circular upregulation of matrix degradation. Conclusion-Our Materials and...

RESUMEN La vitamina C es uno de los antioxidantes más conocidos. Su ingesta ha sido asociada a un sinnúmero de beneficios, algunos de los cuales tienen un sustento científico débil o inexistente. En esta revisión se presentan en forma resumida aspectos biológicos que determinan la homeostasis de la vitamina C y se discute la información disponible sobre sus posibles efectos benéficos y su ingesta, en diversos países con especial énfasis en algunos grupos de riesgo. También se presentan sus efectos benéficos en inflamación, cáncer y enfermedades cardiovasculares, así como su acción de inmunomodulador y regulador epigenético. Se revisan también algunas fuentes dietarias de vitamina C y los factores que influyen en su estabilidad. Terminando con un análisis general de los trabajos relacionados con conducta de vida saludable en países latinoamericanos, que reflejan los malos hábitos alimentarios y que podrían dar cuenta de una hipovitaminosis de vitamina C aún no reportada y repercutir en el desarrollo de envejecimiento precoz y enfermedades crónicas no transmisibles.

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