Disease relevance of PODXL

• A weak positive association was also observed between prostate cancer risk and PODXL variant 340A (in linkage disequilibrium with another variant, 587T) (OR=1.48, 95%CI=1.02-2.14, P=0.04) [1].
• Human embryonal carcinoma tumor antigen, Gp200/GCTM-2, is podocalyxin [2].
• Sinusoidal expression of PODXL1 is also seen in a less diffuse pattern in FNH and adenoma [3].
• PODXL1 is expressed in tumour-associated microvasculature endothelial cells in HCC, as well as in capillarized sinusoidal endothelium of focal nodular hyperplasia (FNH) and hepatic adenoma [3].
• Podocalyxin-like protein 1 expression is useful to differentiate pancreatic ductal adenocarcinomas from adenocarcinomas of the biliary and gastrointestinal tracts [4].
• We report here that purified podocalyxin from embryonal carcinoma has binding activity with the TRA-1-60 and TRA-1-81 antibodies [5].

High impact information on PODXL

• Identification of podocalyxin-like protein as a high endothelial venule ligand for L-selectin: parallels to CD34 [6].
• PCLP has been shown previously to be expressed on the foot processes of podocytes in the kidney glomerulus as well as on vascular endothelium at some sites [6].
• Furthermore, purified HEV-derived PCLP is able to support the tethering and rolling of lymphocytes under physiological flow conditions in vitro [6].
• These results implicate PODXL as a candidate prostate cancer tumor aggressiveness gene mapping to chromosome 7q32-q33 [1].
• DNA from probands of linked families was examined for germ-line mutations in PODXL [1].

Biological context of PODXL

• The smallest region of allelic imbalance contains the podocalyxin-like (PODXL) gene, which we evaluate here as a candidate prostate cancer aggressiveness gene mapping to 7q32-q33 [1].
• PODXL is also transcriptionally regulated by WT1 and has roles in cell adhesion and anti-adhesion [7].
• The extracellular domain contains multiple potential sites for N- and O-linked glycosylation and 4 cysteines for potential disulfide bonding similar to rabbit PCLP1 [8].
• Human renal cortex and heart cDNA libraries were screened for a human homolog of rabbit PCLP1 using the rabbit PCLP1 cDNA as a probe [8].
• Gp200 is remarkably similar to another embryonal carcinoma antigen, GCTM-2, a cell differentiation marker that is also detected in blood of testis cancer patients, yet neither molecular identity is known [2].

Anatomical context of PODXL

• The presence of CD34+ and PODXL1+ sinusoidal endothelial cells aids in the diagnosis of HCC [3].
• Podocalyxin-like protein 1 (PODXL-1) is expressed on vascular endothelium, hematopoietic precursor cells, and renal podocytes [4].
• A model of inflammatory glomerular injury induced by guinea pig anti-rabbit basement membrane (anti-GBM) antibody was used to examine the distribution and amount of GLEPP1 and PCLP1 mRNA and protein [9].
• Surprisingly, PCLP protein was not detected in any mature blood cells [10].
• These results suggest that human PCLP may be a valuable marker for a subset of haematopoietic stem cells [10].

Associations of PODXL with chemical compounds

• Podocalyxin-like protein (PCLP) is a transmembrane sialomucin that is similar in structure to the well-characterized L-selectin ligand CD34 [6].
• Among eight selectin L ligands examined, podocalyxin-like, mucosal addressin cell adhesion molecule-1 (MADCAM1) and chondroitin sulfate proteoglycan 2 (CSPG2) were localized in the endometrial endothelium [11].
• The carboxy-terminal intracellular domain of podxl is nearly 100% identical in most species; however, the ectodomain shows considerable variations although the cysteine residues are conserved [12].
• A correlation was found between the degree of methylation of the CpG promoter dinucleotides and the rate of podxl expression in different cell lines [13].

Other interactions of PODXL

• A preferred target of p53-mediated repression in this system is the podocalyxin (PODXL) gene [7].
• Expression of PODXL1 was compared with anti-CD34, CD31 and von Willebrand factor VIII staining by immunohistochemistry [3].
• Glomerular epithelial protein 1 and podocalyxin-like protein 1 in inflammatory glomerular disease (crescentic nephritis) in rabbit and man [9].
• Moreover, double-immunolabeling and serial-section analysis provided evidence that CKIs and markers specific for differentiating podocytes, namely PHM-5 (podocalyxin-like protein in humans), synaptopodin (a foot process-related protein), and C3b receptor, were co-expressed at the capillary-loop stage [14].
• Studies conducted to localize the protein products of these genes by immunohistochemical staining of tissue arrays with up to 350 cores of tissues, and by in situ hybridization led to the discovery of novel sinusoidal endothelial cell markers in hepatocellular carcinoma: podocalyxin-like and regulator of G protein signaling-5 [15].

Analytical, diagnostic and therapeutic context of PODXL

• Molecular cloning and characterization of human podocalyxin-like protein. Orthologous relationship to rabbit PCLP1 and rat podocalyxin [8].
• By Northern blotting and cDNA sequencing, the haematopoietic and renal PCLP mRNAs were identical [10].

References