caa a22 4500 445797444 CHVBK 20180317145130.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10620-010-1314-2 doi (NATIONALLICENCE)springer-10.1007/s10620-010-1314-2 Colorectal Cancer in the Cotton Top Tamarin ( Saguinus oedipus ): How Do They Evade Liver Metastasis? [Elektronische Daten] [Martin Tobi, Mijin Kim, Regis Zimmer, James Hatfield, Michael Kam, Nabiha Khoury, Angela Carville, Michael Lawson, William Schiemann, Peter Thomas] Background and Aim: A major cause of cancer-related deaths is the development of liver metastasis. To better understand the metastatic process, we studied the cotton top tamarin as an animal model, which spontaneously develops colorectal cancer but rarely liver metastasis. Method: DNA was extracted from primates and Hot-Start PCR was performed. Sequencing was achieved with Big-Dye Terminator™ Sequencing Kit. Tissue expression and glycosylation studies were also performed for carcinoembryonic antigen family proteins. Results: Sixty-three percent of tamarin carcinoembryonic antigen had PELPK changes essential for carcinoembryonic antigen hepatic uptake. Tamarin carcinoembryonic antigen showed minimal glycosylation. Cotton top tamarin livers showed reduced carcinoembryonic antigen-receptor expression and were devoid of CEACAM1 (BGP) as compared to human liver despite positive expression in cotton top tamarin gallbladder mucosa. Peritumoral regions showed more CEACAM1 in human hepatocyte cytoplasm than in biliary canaliculi (P<0.05). Therefore, tamarins may evade liver metastasis through mechanisms of decreased hepatic uptake by altered PELPK sequences, reduced glycosylation and reduced carcinoembryonic antigen-receptor expression. Furthermore, the absence of cotton top tamarin hepatocyte CEACAM1 may lead to alteration of the liver milieu creating an inhospitable "infertile-field” for metastases. Conclusions: Four hypotheses explain a complex mechanism for the lack of liver metastasis: (1) carcinoembryonic antigen PELPK-encoding nucleotide sequence changes, (2) minimal carcinoembryonic antigen glycosylation, (3) reduced carcinoembryonic antigen-receptor expression, and (4) reduced CEACAM1 distribution, a putative vascular endothelial growth factor. While these hypotheses are not necessarily causal they are testable and therefore are feasible targets for prevention of hepatic metastasis in man. US Government, 2010 Cotton top tamarin nationallicence Carcinoembryonic antigen nationallicence CEACAM1 nationallicence Sequencing nationallicence Metastasis nationallicence Tobi Martin Department of Medicine and Pathology, VAMC and Wayne State University, Detroit, MI, USA aut Kim Mijin Gastroenterology Division, University of Pennsylvania, Philadelphia, PA, USA aut Zimmer Regis Department of Surgery, Boston University, Boston, MA, USA aut Hatfield James Department of Medicine and Pathology, VAMC and Wayne State University, Detroit, MI, USA aut Kam Michael Department of Medicine and Pathology, VAMC and Wayne State University, Detroit, MI, USA aut Khoury Nabiha Department of Medicine and Pathology, VAMC and Wayne State University, Detroit, MI, USA aut Carville Angela New England Primate Center, Boston, MA, USA aut Lawson Michael Kaiser Permanente Medical Center, Sacramento, CA, USA aut Schiemann William Department of Pharmacology, University of Colorado, Aurora, CO, USA aut Thomas Peter Department of Surgery, Boston University, Boston, MA, USA aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 397-405 0163-2116 56:2<397 2011 56 10620 https://doi.org/10.1007/s10620-010-1314-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1314-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tobi Martin Department of Medicine and Pathology, VAMC and Wayne State University, Detroit, MI, USA aut NATIONALLICENCE 700 1- Kim Mijin Gastroenterology Division, University of Pennsylvania, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Zimmer Regis Department of Surgery, Boston University, Boston, MA, USA aut NATIONALLICENCE 700 1- Hatfield James Department of Medicine and Pathology, VAMC and Wayne State University, Detroit, MI, USA aut NATIONALLICENCE 700 1- Kam Michael Department of Medicine and Pathology, VAMC and Wayne State University, Detroit, MI, USA aut NATIONALLICENCE 700 1- Khoury Nabiha Department of Medicine and Pathology, VAMC and Wayne State University, Detroit, MI, USA aut NATIONALLICENCE 700 1- Carville Angela New England Primate Center, Boston, MA, USA aut NATIONALLICENCE 700 1- Lawson Michael Kaiser Permanente Medical Center, Sacramento, CA, USA aut NATIONALLICENCE 700 1- Schiemann William Department of Pharmacology, University of Colorado, Aurora, CO, USA aut NATIONALLICENCE 700 1- Thomas Peter Department of Surgery, Boston University, Boston, MA, USA aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/2(2011-02-01), 397-405 0163-2116 56:2<397 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer