Disease relevance of PDPN

• Although podoplanin was primarily absent from normal human epidermis, its expression was strongly induced in 22 of 28 squamous cell carcinomas studied [1].
• We found that expression level of aggrus was enhanced in most colorectal tumor patients [2].
• 1. Podoplanin was also strongly expressed by granulosa cells in normal ovarian follicles, and by ovarian dysgerminomas and granulosa cell tumors [1].
• The mucin-type glycoprotein podoplanin is specifically expressed by lymphatic but not blood vascular endothelial cells in culture and in tumor-associated lymphangiogenesis, and podoplanin deficiency results in congenital lymphedema and impaired lymphatic vascular patterning [1].
• To examine a potential role for PDPN in testicular neoplasms and during testicular development, we investigated its expression pattern during the development of human testis and in a series of testicular CIS, gonadoblastoma and overt germ-cell tumours [3].

Psychiatry related information on PDPN

• The results demonstrated an association of aggressiveness with reduced 5-HT1A receptor expression and function, thereby providing support for the view favoring the idea that brain HT1A receptor contributes to the genetically defined individual differences in aggressiveness [4].
• LVD assessment by podoplanin immunohistochemistry may become a useful predictor of LN metastasis in T1 early gastric cancer and may influence the decision making process for additional surgery [5].

High impact information on PDPN

• In general, glycoprotein 36 was more abundantly expressed on fresh (uncultured) leukemia-lymphoma cells than on cultured leukemia-lymphoma cell lines [6].
• We now demonstrate that this is a general phenomenon; cells that co-stain for the macrophage marker F4/80 and the lymphatic markers LYVE-1 (lymphatic vascular endothelium hyaluronate receptor) and podoplanin contribute to lymphatic vessels in full-thickness wounds [7].
• In addition, lung metastasis resulting from Aggrus expression decreased the survival of the mice [8].
• By generating several Aggrus point mutants, we revealed that point mutation at the platelet aggregation-stimulating domain of Aggrus (Thr34 and Thr52) obliterated both platelet aggregation and metastasis [8].
• Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors [1].

Chemical compound and disease context of PDPN

• The mean width of the podocyte foot processes was inversely correlated with the protein levels of nephrin (r = -0.443, P < 0.05), whereas it was positively correlated with podoplanin mRNA levels (r = 0.468, P < 0.05) and proteinuria (r = 0.585, P = 0.001) [9].
• METHODS: Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer [10].
• Quality of voice after treatment for T1A glottic squamous cell carcinoma was studied in two matched groups of males treated either with CO2 laser cordectomi (n = 18, mean age 65.2 years) or with full dose radiotherapy (n = 18, mean age 65.1 years) [11].

Biological context of PDPN

• Expression of mouse Aggrus and its human homologue (also known as T1alpha-2/gp36) induced platelet aggregation without requiring plasma components [2].
• These findings suggest a potential role of podoplanin in tumor progression, and they also identify the first commercially available antibody for the specific staining of a defined lymphatic marker in archival human tissue sections, thereby enabling more widespread studies of tumor lymphangiogenesis in human cancers [1].
• Here we report that the periductal CT is populated by two distinct cell phenotypes; one expressing podoplanin, a protein otherwise found on lymph endothelia and on epithelia involved in fluid fluxes, and a second expressing a fibroblast marker [12].
• In a recent genome-wide gene expression screening using cDNA microarrays, we found PDPN over-expressed in CIS compared to normal adult testis [3].
• CONCLUSION: These data establish that in human osteoblast-like MG63 cells, Sp1 and Sp3 stimulate basal PDPN transcription in a concerted, yet independent manner, whereas Saos-2 cells lack sufficient nuclear Sp protein amounts for transcriptional activation [13].

Anatomical context of PDPN

• We found that, in addition to lymphatic endothelium, podoplanin was also expressed by peritoneal mesothelial cells, osteocytes, glandular myoepithelial cells, ependymal cells, and by stromal reticular cells and follicular dendritic cells of lymphoid organs [1].
• Ectopic expression of human PA2.26 in HeLa carcinoma cells and immortalized HaCaT keratinocytes promoted a redistribution of ezrin to the cell edges, the formation of cell-surface protrusions and reduced Ca(2+)-dependent cell-cell adhesiveness [14].
• The human PA2.26 gene is expressed as 2 transcripts of 0.9 and 2.7 kb in several normal tissues, such as the placenta, skeletal muscle, heart and lung [14].
• An interstitial network of podoplanin-expressing cells in the human endolymphatic duct [12].
• A new anti-human Aggrus monoclonal antibody, YM-1, was established to detect the expression of human Aggrus on these CHO cell mutants [15].

Associations of PDPN with chemical compounds

• We report the full cDNA sequence encoding the human homologue of murine PA2.26 (T1alpha-2, podoplanin), a small mucin-type transmembrane glycoprotein originally identified as a cell-surface antigen induced in keratinocytes during mouse skin carcinogenesis [14].
• Concomitantly, treatment with the DNA methyltransferase inhibitor 5-azaCdR in combination with trichostatin A (TSA) downregulated podoplanin mRNA levels in MG63 cells, and region-specific in vitro methylation of the distal promoter suggested that DNA methylation rather enhanced than hindered PDPN transcription in both cell types [13].
• Following reduction of T1A Cu(II), another ET process takes place between RSSR(-) and T1B copper(II) of domain 4 with a rate constant of 3.9 +/- 0 [16].
• Real-time PCR was used to determine the mRNA levels of nephrin, podocin, and podoplanin in microdissected glomeruli [9].
• EXPERIMENTAL DESIGN: Serial sections of 10 IBCs and 10 non-IBCs were immunostained for D2-40, LYVE-1, podoplanin, and PROX-1 [17].

Physical interactions of PDPN

• Here, we found that human podoplanin directly interacts with ezrin (and moesin) in vitro and in vivo through a cluster of basic amino acids within its cytoplasmic tail, mainly through a juxtamembrane dipeptide RK [18].

Co-localisations of PDPN

• In normal skin and kidney, podoplanin colocalized with vascular endothelial growth factor receptor-3, the only other lymphatic marker presently available [19].

Other interactions of PDPN

• A majority of the interstitial cells expressed podoplanin but not the lymphatic endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial growth factor receptor-3 (VEGFR-3) [12].
• Immunohistochemistry was performed using antibodies to two recently identified markers of lymphatic endothelium, namely, LYVE-1 and podoplanin, and to the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C [20].
• By contrast, blood vessel endothelium and hemangiomas were strongly positive for PAL-E and CD34 but were mostly negative for CD9 and podoplanin [21].
• Using sorted cells, we show that LEC but not BEC constitutively express IL-3, which regulates Prox-1 and podoplanin expression in LEC [22].
• We have generated monoclonal antibodies to human D6 and showed D6 immunoreactivity on the ECs lining afferent lymphatics, confirmed as such by staining serial skin sections with antibodies against podoplanin, a known lymphatic EC marker [23].

Analytical, diagnostic and therapeutic context of PDPN

• We generated a human podoplanin-Fc fusion protein and found that the commercially available mouse monoclonal antibody D2-40 specifically recognized human podoplanin, as assessed by enzyme-linked immunosorbent assay and Western blot analyses [1].
• We established by RT-PCR and by immunohistochemistry with a gp36 antibody that PDPN mRNA and the protein product were expressed in testes with germ-cell neoplasms but not in the normal adult testis [3].
• Weak PDPN promoter activity of Saos-2 cells correlated with low Sp1/Sp3 nuclear levels, which was confirmed by Sp1/Sp3 chromatin immunoprecipitations in vivo [13].
• Podoplanin specifically immunolabeled endothelia of benign tumorous lesions of undisputed lymphatic origin (lymphangiomas, hygromas) and was detected there as a 38-kd protein by immunoblotting [19].
• By immunostaining for podoplanin, a novel marker for lymphatic endothelium, and for factor VIII-related antigen, we determined lymphatic and blood vessel invasion in tissue samples of 98 patients with cervical cancer pT1b treated by radical hysterectomy [24].

References