Podocalyxin enhances the adherence of cells to platelets
CELLULAR AND MOLECULAR LIFE SCIENCES
Authors: Larrucea, S.; Butta, N.; Rodriguez, R. B.; Alonso-Martin, S.; Arias-Salgado, E. G.; Ayuso, M. S.; Parrilla, R.
Abstract
Podocalyxin (PODXL) is a mucin protein of the CD34 family expressed in kidney glomerular podocytes, vascular endothelium, progenitor bone marrow and tumor cells. It is assumed that PODXL plays an anti-adherent role in kidney podocytes. CHO cells stably expressing human PODXL (CHOPODXL) or human tumor cells (Tera-1) inherently expressing PODXL showed increased adherence to platelets. The adherence of cells was inhibited (70 %) by blockers of platelet P-selectin, prevented by the soluble ectodomain of human PODXL (PODXL-A) or by the arginine-glycine-aspartate (RGDS) peptide and partially impeded by inhibition of integrin alpha V beta 3/ aVP5, suggesting a coordinated action of P-selectin and integrins. Colocalization of platelet P-selectin and PODXL expressed on CHO cells was demonstrated by confocal immunofluorescence. No adherence to platelets was observed when PODXL was expressed in glycomutant CHO cells deficient in sialic acid.
Podocalyxin-like protein 1 expression is useful to differentiate pancreatic ductal adenocarcinomas from adenocarcinomas of the biliary and gastrointestinal tracts
HUMAN PATHOLOGY
Authors: Ney, Jasmin Teresa; Zhou, Hui; Sipos, Bence; Buettner, Reinhard; Chen, Xin; Kloeppel, Guenter; Guetgemann, Ines
Abstract
Metastases of adenocarcinomas from the pancreas, liver, and gastrointestinal tract are difficult to distinguish from each other because of their similar morphological and immunohistochemical features. So far, no specific marker for pancreatic ductal adenocarcinomas has been described. Podocalyxin-like protein 1 (PODXL-1) is expressed on vascular endothelium, hematopoietic precursor cells, and renal podocytes. We found that 44% (71/160) of pancreatic ductal adenocarcinomas expressed PODXL-1 in a membranous pattern. There was no expression in intrahepatic cholangiocarcinomas (0/18, P < .001), rarely in adenocarcinomas of the extrahepatic bile ducts (1/13, P = .009), and none in duodenal adenocarcinomas (0/5, P = .070). PODXL-1 expression was seen in only 9% of hepatocellular carcinomas (5/56, P < .001), 9% (4/47, P < .001) of gastric carcinomas, 10% of esophageal adenocarcinomas (2/20, P = .003), and 6% of colonic adenocarcinomas (1/17, P = .001). When used as a differential diagnostic marker, ampullary carcinoma needs to be excluded, as 30% (6/20, P = .24) of ampullary carcinomas stain positive, especially those of the signet-ring type (3/3). Adenocarcinomas of the lung and prostate, and liver metastases of colorectal carcinomas lacked PODXL-1 expression. It is concluded that immunoreactivity for PODXL-1 favors a pancreatic origin if ampullary carcinoma is excluded. (c) 2007 Elsevier Inc. All rights reserved.