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{{Infobox_gene}}
{{PBB_Controls
'''Podoplanin''' is a [[protein]] that is encoded by the "PDPN" gene in humans and animals.<ref name="pmid10393083">{{cite journal |vauthors=Zimmer G, Oeffner F, Von Messling V, Tschernig T, Groness HJ, Klenk HD, Herrler G | title = Cloning and characterization of gp36, a human mucin-type glycoprotein preferentially expressed in vascular endothelium | journal = Biochem J | volume = 341 | issue =  Pt 2| pages = 277–84 |date=Sep 1999 | pmid = 10393083 | pmc = 1220357 | doi =  10.1042/0264-6021:3410277}}</ref><ref name="pmid9651190">{{cite journal |vauthors=Ma T, Yang B, Matthay MA, Verkman AS | title = Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a water channel or a regulator of aquaporin-type water channels | journal = Am J Respir Cell Mol Biol | volume = 19 | issue = 1 | pages = 143–9 |date=Jul 1998 | pmid = 9651190 | pmc = | doi =  10.1165/ajrcmb.19.1.2953}}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PDPN podoplanin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10630| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure and function ==
{{GNF_Protein_box
Podoplanin is a [[mucin]]-type protein with a mass of 36- to 43-kDa. It is relatively well conserved between species, with homologues in humans, mice, rats, dogs and hamsters.<ref name="pmid22988448">{{cite journal|last1=Astarita|first1=JL|last2=Acton|first2=SE|last3=Turley|first3=SJ|title=Podoplanin: emerging functions in development, the immune system, and cancer.|journal=Frontiers in Immunology|date=2012|volume=3|pages=283|pmid=22988448|doi=10.3389/fimmu.2012.00283|pmc=3439854}}</ref>
| image =
| image_source =
| PDB =  
| Name = Podoplanin
| HGNCid = 29602
| Symbol = PDPN
| AltSymbols =; GP40; GP36; Gp38; HT1A-1; OTS8; PA2.26; T1A; T1A-2
| OMIM = 608863
| ECnumber = 
| Homologene = 4729
| MGIid = 103098
| GeneAtlas_image1 = PBB_GE_PDPN_221898_at_tn.png
| GeneAtlas_image2 = PBB_GE_PDPN_204879_at_tn.png
| Function = {{GNF_GO|id=GO:0008517 |text = folic acid transporter activity}} {{GNF_GO|id=GO:0015171 |text = amino acid transmembrane transporter activity}} {{GNF_GO|id=GO:0015250 |text = water channel activity}}
| Component = {{GNF_GO|id=GO:0001726 |text = ruffle}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}} {{GNF_GO|id=GO:0030027 |text = lamellipodium}} {{GNF_GO|id=GO:0030175 |text = filopodium}}
| Process = {{GNF_GO|id=GO:0000902 |text = cell morphogenesis}} {{GNF_GO|id=GO:0001946 |text = lymphangiogenesis}} {{GNF_GO|id=GO:0006833 |text = water transport}} {{GNF_GO|id=GO:0006865 |text = amino acid transport}} {{GNF_GO|id=GO:0007275 |text = multicellular organismal development}} {{GNF_GO|id=GO:0008360 |text = regulation of cell shape}} {{GNF_GO|id=GO:0015884 |text = folic acid transport}} {{GNF_GO|id=GO:0030324 |text = lung development}} {{GNF_GO|id=GO:0051272 |text = positive regulation of cell motility}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 10630
    | Hs_Ensembl = ENSG00000162493
    | Hs_RefseqProtein = NP_001006625
    | Hs_RefseqmRNA = NM_001006624
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 13782814
    | Hs_GenLoc_end = 13817039
    | Hs_Uniprot = Q86YL7
    | Mm_EntrezGene = 14726
    | Mm_Ensembl = ENSMUSG00000028583
    | Mm_RefseqmRNA = XM_992534
    | Mm_RefseqProtein = XP_997628
    | Mm_GenLoc_db =
    | Mm_GenLoc_chr = 4
    | Mm_GenLoc_start = 142534123
    | Mm_GenLoc_end = 142566141
    | Mm_Uniprot = Q62011
  }}
}}
'''Podoplanin''', also known as '''PDPN''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PDPN podoplanin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10630| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a type-I, integral membrane, heavily O-[[glycosylated]] [[glycoprotein]] with diverse distribution in human tissues. The physiological function of this protein may be related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor. The specific function of this protein has not been determined but it has been proposed as a marker of lung injury. Alternatively spliced transcript variants encoding different isoforms have been identified.<ref name="entrez" />
{{PBB_Summary
 
| section_title =
This protein has been found to have functions in lung alveolar cells, kidney podocytes, and lymphatic endothelial cells. More recently, this protein has been found in neural tissue in both mouse and human samples.<ref name="pmid18924607">{{cite journal |vauthors=Fu J, Gerhardt H, McDaniel JM, Xia B, Liu X, Ivanciu L, Ny A, Hermans K, Silasi-Mansat R, McGee S, Nye E, Ju T, Ramirez MI, Carmeliet P, Cummings RD, Lupu F, Xia L | title = Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice | journal = J. Clin. Invest. | volume = 118 | issue = 11 | pages = 3725–37 |date=November 2008 | pmid = 18924607 | pmc = 2567837 | doi = 10.1172/JCI36077 | url = }}</ref>
| summary_text = This gene encodes a type-I integral membrane glycoprotein with diverse distribution in human tissues. The physiological function of this protein may be related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor. The specific function of this protein has not been determined but it has been proposed as a marker of lung injury. Alternatively spliced transcript variants encoding different isoforms have been identified.<ref name="entrez">{{cite web | title = Entrez Gene: PDPN podoplanin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10630| accessdate = }}</ref>
 
}}
In lymphatic endothelial cells, experimentation has indicated that podoplanin plays a role in proper formation of linkages between the cardiovascular system and the lymphatic systems, typically causing fatty liver disease in these mice.<ref name="pmid18924607"/>
 
Although the exact function is unknown in many tissues, podoplanin is generally receptive to detection via immunofluorescent staining and has been shown to co-localize with the protein [[nestin (protein)|nestin]], a type VI intermediate filament protein expressed almost primarily in neural tissues.<ref name="pmid21060740">{{cite journal |vauthors=Imaizumi Y, Amano I, Tsuruga E, Kojima H, Sawa Y | title = Immunohistochemical examination for the distribution of podoplanin-expressing cells in developing mouse molar tooth germs | journal = Acta Histochem Cytochem | volume = 43 | issue = 5 | pages = 115–21 |date=October 2010 | pmid = 21060740 | doi = 10.1267/ahc.10023 | pmc=2965832}}</ref> Currently, the only protein known to interact with podoplanin physiologically is [[CLEC-2]], a C-type lectin 2 expressed on platelets and on [[hematopoietic cell]]s.<ref>{{cite journal|last1=Herzog|first1=BH|last2=Fu|first2=J|last3=Wilson|first3=SJ|last4=Hess|first4=PR|last5=Sen|first5=A|last6=McDaniel|first6=JM|last7=Pan|first7=Y|last8=Sheng|first8=M|last9=Yago|first9=T|last10=Silasi-Mansat|first10=R|last11=McGee|first11=S|last12=May|first12=F|last13=Nieswandt|first13=B|last14=Morris|first14=AJ|last15=Lupu|first15=F|last16=Coughlin|first16=SR|last17=McEver|first17=RP|last18=Chen|first18=H|last19=Kahn|first19=ML|last20=Xia|first20=L|title=Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2.|journal=Nature|date=3 October 2013|volume=502|issue=7469|pages=105–9|pmid=23995678|doi=10.1038/nature12501|pmc=3791160}}</ref> Both serve a role in the proper formation of blood/lymphatic connections in embryonic development.
 
== Clinical significance ==
PDPN has been studied extensively in the cancer field. It is a specific lymphatic vessel marker, and since lymphangiogenesis levels are correlated with poor prognosis in cancer patients, it can be used as a diagnostic marker.<ref name="pmid22988448"/> It is often upregulated in certain types of cancer, including several types of [[squamous cell carcinoma]]s, malignant [[mesothelioma]] and [[brain tumor]]s.<ref name="pmid22988448"/> Moreover, it can be upregulated by cancer-associated fibroblasts (CAFs) in the tumor stroma,<ref name="pmid22988448"/><ref>{{cite journal|last1=Kitano|first1=H|last2=Kageyama|first2=S|last3=Hewitt|first3=SM|last4=Hayashi|first4=R|last5=Doki|first5=Y|last6=Ozaki|first6=Y|last7=Fujino|first7=S|last8=Takikita|first8=M|last9=Kubo|first9=H|last10=Fukuoka|first10=J|title=Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient survival.|journal=Archives of pathology & laboratory medicine|date=October 2010|volume=134|issue=10|pages=1520–7|pmid=20923309|doi=10.1043/2009-0114-OA.1}}</ref> where it has been associated with poor prognosis.<ref>{{cite journal|last1=Chuang|first1=WY|last2=Yeh|first2=CJ|last3=Chao|first3=YK|last4=Liu|first4=YH|last5=Chang|first5=YS|last6=Tseng|first6=CK|last7=Chang|first7=HK|last8=Wan|first8=YL|last9=Hsueh|first9=C|title=Concordant podoplanin expression in cancer-associated fibroblasts and tumor cells is an adverse prognostic factor in esophageal squamous cell carcinoma.|journal=International Journal of Clinical and Experimental Pathology|date=2014|volume=7|issue=8|pages=4847–56|pmid=25197355|pmc=4152045}}</ref>
 
In squamous cell carcinomas, PDPN is believed to play a key role in the cancer cell invasiveness by controlling [[invadopodia]], and thus mediating efficient [[Extracellular matrix|ECM]] degradation.<ref>{{cite journal|last1=Martín-Villar|first1=E|last2=Borda-d'Agua|first2=B|last3=Carrasco-Ramirez|first3=P|last4=Renart|first4=J|last5=Parsons|first5=M|last6=Quintanilla|first6=M|last7=Jones|first7=GE|title=Podoplanin mediates ECM degradation by squamous carcinoma cells through control of invadopodia stability.|journal=Oncogene|date=20 August 2015|volume=34|issue=34|pages=4531–44|pmid=25486435|doi=10.1038/onc.2014.388|pmc=4430312}}</ref>


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  |vauthors=Wicki A, Christofori G |title=The potential role of podoplanin in tumour invasion |journal=Br. J. Cancer |volume=96 |issue= 1 |pages= 1–5 |year= 2007 |pmid= 17179989 |doi= 10.1038/sj.bjc.6603518 | pmc=2360213 }}
| citations =
*{{cite journal   |vauthors=Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, etal |title=Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening |journal=Genomics |volume=23 |issue= 1 |pages= 42–50 |year= 1995 |pmid= 7829101 |doi= 10.1006/geno.1994.1457 }}
*{{cite journal  | author=Wicki A, Christofori G |title=The potential role of podoplanin in tumour invasion. |journal=Br. J. Cancer |volume=96 |issue= 1 |pages= 1-5 |year= 2007 |pmid= 17179989 |doi= 10.1038/sj.bjc.6603518 }}
*{{cite journal  |vauthors=Cross SH, Charlton JA, Nan X, Bird AP |title=Purification of CpG islands using a methylated DNA binding column |journal=Nat. Genet. |volume=6 |issue= 3 |pages= 236–44 |year= 1994 |pmid= 8012384 |doi= 10.1038/ng0394-236 }}
*{{cite journal | author=Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, ''et al.'' |title=Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening. |journal=Genomics |volume=23 |issue= 1 |pages= 42-50 |year= 1995 |pmid= 7829101 |doi= 10.1006/geno.1994.1457 }}
*{{cite journal  |vauthors=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery |journal=Genome Res. |volume=6 |issue= 9 |pages= 791–806 |year= 1997 |pmid= 8889548 |doi=10.1101/gr.6.9.791  }}
*{{cite journal  | author=Cross SH, Charlton JA, Nan X, Bird AP |title=Purification of CpG islands using a methylated DNA binding column. |journal=Nat. Genet. |volume=6 |issue= 3 |pages= 236-44 |year= 1994 |pmid= 8012384 |doi= 10.1038/ng0394-236 }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
*{{cite journal  | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791-806 |year= 1997 |pmid= 8889548 |doi= }}
*{{cite journal   |vauthors=Kato Y, Fujita N, Kunita A, etal |title=Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors |journal=J. Biol. Chem. |volume=278 |issue= 51 |pages= 51599–605 |year= 2004 |pmid= 14522983 |doi= 10.1074/jbc.M309935200 }}
*{{cite journal | author=Ma T, Yang B, Matthay MA, Verkman AS |title=Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a water channel or a regulator of aquaporin-type water channels. |journal=Am. J. Respir. Cell Mol. Biol. |volume=19 |issue= 1 |pages= 143-9 |year= 1998 |pmid= 9651190 |doi=  }}
*{{cite journal   |vauthors=Kaneko M, Kato Y, Kunita A, etal |title=Functional sialylated O-glycan to platelet aggregation on Aggrus (T1alpha/Podoplanin) molecules expressed in Chinese hamster ovary cells |journal=J. Biol. Chem. |volume=279 |issue= 37 |pages= 38838–43 |year= 2004 |pmid= 15231832 |doi= 10.1074/jbc.M407210200 }}
*{{cite journal | author=Zimmer G, Oeffner F, Von Messling V, ''et al.'' |title=Cloning and characterization of gp36, a human mucin-type glycoprotein preferentially expressed in vascular endothelium. |journal=Biochem. J. |volume=341 ( Pt 2) |issue= |pages= 277-84 |year= 1999 |pmid= 10393083 |doi= }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal   |vauthors=Martín-Villar E, Scholl FG, Gamallo C, etal |title=Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas |journal=Int. J. Cancer |volume=113 |issue= 6 |pages= 899–910 |year= 2005 |pmid= 15515019 |doi= 10.1002/ijc.20656 }}
*{{cite journal | author=Kato Y, Fujita N, Kunita A, ''et al.'' |title=Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors. |journal=J. Biol. Chem. |volume=278 |issue= 51 |pages= 51599-605 |year= 2004 |pmid= 14522983 |doi= 10.1074/jbc.M309935200 }}
*{{cite journal   |vauthors=Schacht V, Dadras SS, Johnson LA, etal |title=Up-Regulation of the Lymphatic Marker Podoplanin, a Mucin-Type Transmembrane Glycoprotein, in Human Squamous Cell Carcinomas and Germ Cell Tumors |journal=Am. J. Pathol. |volume=166 |issue= 3 |pages= 913–21 |year= 2005 |pmid= 15743802 |doi= 10.1016/S0002-9440(10)62311-5| pmc=1602360  }}
*{{cite journal | author=Kaneko M, Kato Y, Kunita A, ''et al.'' |title=Functional sialylated O-glycan to platelet aggregation on Aggrus (T1alpha/Podoplanin) molecules expressed in Chinese hamster ovary cells. |journal=J. Biol. Chem. |volume=279 |issue= 37 |pages= 38838-43 |year= 2004 |pmid= 15231832 |doi= 10.1074/jbc.M407210200 }}
*{{cite journal   |vauthors=Otsuki T, Ota T, Nishikawa T, etal |title=Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries |journal=DNA Res. |volume=12 |issue= 2 |pages= 117–26 |year= 2007 |pmid= 16303743 |doi= 10.1093/dnares/12.2.117 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal   |vauthors=Hultgård-Ekwall AK, Mayerl C, Rubin K, etal |title=An Interstitial Network of Podoplanin-Expressing Cells in the Human Endolymphatic Duct |journal=J. Assoc. Res. Otolaryngol. |volume=7 |issue= 1 |pages= 38–47 |year= 2006 |pmid= 16408168 |doi= 10.1007/s10162-005-0021-8 | pmc=2504586 }}
*{{cite journal | author=Martín-Villar E, Scholl FG, Gamallo C, ''et al.'' |title=Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas. |journal=Int. J. Cancer |volume=113 |issue= 6 |pages= 899-910 |year= 2005 |pmid= 15515019 |doi= 10.1002/ijc.20656 }}
*{{cite journal   |vauthors=Dumoff KL, Chu CS, Harris EE, etal |title=Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation |journal=Mod. Pathol. |volume=19 |issue= 5 |pages= 708–16 |year= 2006 |pmid= 16528371 |doi= 10.1038/modpathol.3800580 }}
*{{cite journal | author=Schacht V, Dadras SS, Johnson LA, ''et al.'' |title=Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. |journal=Am. J. Pathol. |volume=166 |issue= 3 |pages= 913-21 |year= 2005 |pmid= 15743802 |doi=  }}
*{{cite journal   |vauthors=Omachi T, Kawai Y, Mizuno R, etal |title=Immunohistochemical demonstration of proliferating lymphatic vessels in colorectal carcinoma and its clinicopathological significance |journal=Cancer Lett. |volume=246 |issue= 1–2 |pages= 167–72 |year= 2007 |pmid= 16574316 |doi= 10.1016/j.canlet.2006.02.013 }}
*{{cite journal  | author=Otsuki T, Ota T, Nishikawa T, ''et al.'' |title=Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. |journal=DNA Res. |volume=12 |issue= 2 |pages= 117-26 |year= 2007 |pmid= 16303743 |doi= 10.1093/dnares/12.2.117 }}
*{{cite journal   |vauthors=Mishima K, Kato Y, Kaneko MK, etal |title=Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression |journal=Acta Neuropathol. |volume=111 |issue= 5 |pages= 483–8 |year= 2007 |pmid= 16596424 |doi= 10.1007/s00401-006-0063-y }}
*{{cite journal  | author=Hultgård-Ekwall AK, Mayerl C, Rubin K, ''et al.'' |title=An interstitial network of podoplanin-expressing cells in the human endolymphatic duct. |journal=J. Assoc. Res. Otolaryngol. |volume=7 |issue= 1 |pages= 38-47 |year= 2006 |pmid= 16408168 |doi= 10.1007/s10162-005-0021-8 }}
*{{cite journal   |vauthors=Wicki A, Lehembre F, Wick N, etal |title=Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton |journal=Cancer Cell |volume=9 |issue= 4 |pages= 261–72 |year= 2006 |pmid= 16616332 |doi= 10.1016/j.ccr.2006.03.010 }}
*{{cite journal | author=Dumoff KL, Chu CS, Harris EE, ''et al.'' |title=Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation. |journal=Mod. Pathol. |volume=19 |issue= 5 |pages= 708-16 |year= 2006 |pmid= 16528371 |doi= 10.1038/modpathol.3800580 }}
*{{cite journal   |vauthors=Gregory SG, Barlow KF, McLay KE, etal |title=The DNA sequence and biological annotation of human chromosome 1 |journal=Nature |volume=441 |issue= 7091 |pages= 315–21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 }}
*{{cite journal | author=Omachi T, Kawai Y, Mizuno R, ''et al.'' |title=Immunohistochemical demonstration of proliferating lymphatic vessels in colorectal carcinoma and its clinicopathological significance. |journal=Cancer Lett. |volume=246 |issue= 1-2 |pages= 167-72 |year= 2007 |pmid= 16574316 |doi= 10.1016/j.canlet.2006.02.013 }}
*{{cite journal   |vauthors=Mishima K, Kato Y, Kaneko MK, etal |title=Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma |journal=Acta Neuropathol. |volume=111 |issue= 6 |pages= 563–8 |year= 2007 |pmid= 16718353 |doi= 10.1007/s00401-006-0033-4 }}
*{{cite journal | author=Mishima K, Kato Y, Kaneko MK, ''et al.'' |title=Increased expression of podoplanin in malignant astrocytic tumors as a novel molecular marker of malignant progression. |journal=Acta Neuropathol. |volume=111 |issue= 5 |pages= 483-8 |year= 2007 |pmid= 16596424 |doi= 10.1007/s00401-006-0063-y }}
*{{cite journal | author=Wicki A, Lehembre F, Wick N, ''et al.'' |title=Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. |journal=Cancer Cell |volume=9 |issue= 4 |pages= 261-72 |year= 2006 |pmid= 16616332 |doi= 10.1016/j.ccr.2006.03.010 }}
*{{cite journal | author=Gregory SG, Barlow KF, McLay KE, ''et al.'' |title=The DNA sequence and biological annotation of human chromosome 1. |journal=Nature |volume=441 |issue= 7091 |pages= 315-21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 }}
*{{cite journal | author=Mishima K, Kato Y, Kaneko MK, ''et al.'' |title=Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma. |journal=Acta Neuropathol. |volume=111 |issue= 6 |pages= 563-8 |year= 2007 |pmid= 16718353 |doi= 10.1007/s00401-006-0033-4 }}
}}
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Revision as of 15:21, 11 November 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Podoplanin is a protein that is encoded by the "PDPN" gene in humans and animals.[1][2][3]

Structure and function

Podoplanin is a mucin-type protein with a mass of 36- to 43-kDa. It is relatively well conserved between species, with homologues in humans, mice, rats, dogs and hamsters.[4]

This gene encodes a type-I, integral membrane, heavily O-glycosylated glycoprotein with diverse distribution in human tissues. The physiological function of this protein may be related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor. The specific function of this protein has not been determined but it has been proposed as a marker of lung injury. Alternatively spliced transcript variants encoding different isoforms have been identified.[3]

This protein has been found to have functions in lung alveolar cells, kidney podocytes, and lymphatic endothelial cells. More recently, this protein has been found in neural tissue in both mouse and human samples.[5]

In lymphatic endothelial cells, experimentation has indicated that podoplanin plays a role in proper formation of linkages between the cardiovascular system and the lymphatic systems, typically causing fatty liver disease in these mice.[5]

Although the exact function is unknown in many tissues, podoplanin is generally receptive to detection via immunofluorescent staining and has been shown to co-localize with the protein nestin, a type VI intermediate filament protein expressed almost primarily in neural tissues.[6] Currently, the only protein known to interact with podoplanin physiologically is CLEC-2, a C-type lectin 2 expressed on platelets and on hematopoietic cells.[7] Both serve a role in the proper formation of blood/lymphatic connections in embryonic development.

Clinical significance

PDPN has been studied extensively in the cancer field. It is a specific lymphatic vessel marker, and since lymphangiogenesis levels are correlated with poor prognosis in cancer patients, it can be used as a diagnostic marker.[4] It is often upregulated in certain types of cancer, including several types of squamous cell carcinomas, malignant mesothelioma and brain tumors.[4] Moreover, it can be upregulated by cancer-associated fibroblasts (CAFs) in the tumor stroma,[4][8] where it has been associated with poor prognosis.[9]

In squamous cell carcinomas, PDPN is believed to play a key role in the cancer cell invasiveness by controlling invadopodia, and thus mediating efficient ECM degradation.[10]

References

  1. ↑ Zimmer G, Oeffner F, Von Messling V, Tschernig T, Groness HJ, Klenk HD, Herrler G (Sep 1999). "Cloning and characterization of gp36, a human mucin-type glycoprotein preferentially expressed in vascular endothelium". Biochem J. 341 (Pt 2): 277–84. doi:10.1042/0264-6021:3410277. PMC 1220357. PMID 10393083.
  2. ↑ Ma T, Yang B, Matthay MA, Verkman AS (Jul 1998). "Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a water channel or a regulator of aquaporin-type water channels". Am J Respir Cell Mol Biol. 19 (1): 143–9. doi:10.1165/ajrcmb.19.1.2953. PMID 9651190.
  3. ↑ 3.0 3.1 "Entrez Gene: PDPN podoplanin".
  4. ↑ 4.0 4.1 4.2 4.3 Astarita, JL; Acton, SE; Turley, SJ (2012). "Podoplanin: emerging functions in development, the immune system, and cancer". Frontiers in Immunology. 3: 283. doi:10.3389/fimmu.2012.00283. PMC 3439854. PMID 22988448.
  5. ↑ 5.0 5.1 Fu J, Gerhardt H, McDaniel JM, Xia B, Liu X, Ivanciu L, Ny A, Hermans K, Silasi-Mansat R, McGee S, Nye E, Ju T, Ramirez MI, Carmeliet P, Cummings RD, Lupu F, Xia L (November 2008). "Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice". J. Clin. Invest. 118 (11): 3725–37. doi:10.1172/JCI36077. PMC 2567837. PMID 18924607.
  6. ↑ Imaizumi Y, Amano I, Tsuruga E, Kojima H, Sawa Y (October 2010). "Immunohistochemical examination for the distribution of podoplanin-expressing cells in developing mouse molar tooth germs". Acta Histochem Cytochem. 43 (5): 115–21. doi:10.1267/ahc.10023. PMC 2965832. PMID 21060740.
  7. ↑ Herzog, BH; Fu, J; Wilson, SJ; Hess, PR; Sen, A; McDaniel, JM; Pan, Y; Sheng, M; Yago, T; Silasi-Mansat, R; McGee, S; May, F; Nieswandt, B; Morris, AJ; Lupu, F; Coughlin, SR; McEver, RP; Chen, H; Kahn, ML; Xia, L (3 October 2013). "Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2". Nature. 502 (7469): 105–9. doi:10.1038/nature12501. PMC 3791160. PMID 23995678.
  8. ↑ Kitano, H; Kageyama, S; Hewitt, SM; Hayashi, R; Doki, Y; Ozaki, Y; Fujino, S; Takikita, M; Kubo, H; Fukuoka, J (October 2010). "Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient survival". Archives of pathology & laboratory medicine. 134 (10): 1520–7. doi:10.1043/2009-0114-OA.1. PMID 20923309.
  9. ↑ Chuang, WY; Yeh, CJ; Chao, YK; Liu, YH; Chang, YS; Tseng, CK; Chang, HK; Wan, YL; Hsueh, C (2014). "Concordant podoplanin expression in cancer-associated fibroblasts and tumor cells is an adverse prognostic factor in esophageal squamous cell carcinoma". International Journal of Clinical and Experimental Pathology. 7 (8): 4847–56. PMC 4152045. PMID 25197355.
  10. ↑ Martín-Villar, E; Borda-d'Agua, B; Carrasco-Ramirez, P; Renart, J; Parsons, M; Quintanilla, M; Jones, GE (20 August 2015). "Podoplanin mediates ECM degradation by squamous carcinoma cells through control of invadopodia stability". Oncogene. 34 (34): 4531–44. doi:10.1038/onc.2014.388. PMC 4430312. PMID 25486435.

Further reading

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