An oligopeptide transporter is expressed at high levels in the pancreatic carcinoma cell lines AsPc-1 and Capan-2.
Carcinomas of the exocrine pancreas are poorly understood and have a poor prognosis because of their highly malignant nature. Using two human pancreatic cancer cell lines, AsPc-1 and Capan-2, we have investigated avenues that might be useful in targeting the delivery of antineoplastic agents to such cancers. Qualitative RNA PCRs established the presence of the oligopeptide transporter PEPT 1 in these pancreatic cell lines. Northern analysis confirmed the presence of a 3.3-kb transcript. The transporter is normally expressed primarily in small intestinal epithelial cells for nutrient absorption. It is also expressed in a human intestinal cell line, Caco-2. High levels of PEPT 1 protein expression in AsPc-1 and Capan-2, as multiple glycosylated forms (Mr approximately 90,000-120,000), were confirmed by Western immunoblotting, when compared with Caco-2 cell cultures. Absorption of the model dipeptide glycyl-L-sarcosine by AsPc-1 and Capan-2 cells was similar to glycyl-L-sarcosine absorption by Caco-2 cells and a Chinese hamster ovary cell line expressing human PEPT 1 (CHO-PEPT 1). Uptake was pH dependent and inhibited by several di/tripeptides and bestatin, but it remained unaffected by glycine and tetraglycine. Peptide solute transport by AsPc-1 and Capan-2 cells exhibited binding affinities (Kms) similar to those previously reported for PEPT 1, whereas the transport maximal velocity (Vmax) of the AsPc-1 cells was much greater than those of the Capan-2 and Caco-2 cells. Immunomicroscopy demonstrated PEPT 1 protein localized at the plasma membrane and in intracellular vesicular structures, similar to that observed for Caco-2 and CHO-PEPT 1 cells. These data suggest that the pancreatic cancer cells AsPc-1 and Capan-2 express surprisingly high levels of a solute transporter that was previously thought to be restricted in function to the absorption of nutrients from the small intestine.[1]References
- An oligopeptide transporter is expressed at high levels in the pancreatic carcinoma cell lines AsPc-1 and Capan-2. Gonzalez, D.E., Covitz, K.M., Sadée, W., Mrsny, R.J. Cancer Res. (1998) [Pubmed]
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