PDPN Membrane Protein Introduction

Introduction of PDPN

Podoplanin (PDPN), encoded by human PDPN gene, is a 38-40 kDa type I mucin-like transmembrane glycoprotein belonging to the podoplanin family. The structure of PDPN is characterized by a heavily glycosylated amino-terminal extracellular domain of approximately 130 amino acids, followed by a single transmembrane domain of approximately 25 amino acids, and a short intracellular domain of approximately 10 amino acids. PDPN has been found to be expressed in numerous human issues, such as the kidney, skeletal muscles, heart, placenta, and lung. Because of the exclusive expression in the lymphatic endothelial cells (LEC), PDPN has been regarded as a useful marker for lymphatic endothelium and lymphangiogenesis.

Function of PDPN Membrane Protein

Except for the role as a specific marker of lymphatic endothelium, PDPN is widely reported as an effective biomarker and therapeutic target of various cancers. Recent studies show that PDPN expression is upregulated in various human tumors, including colorectal tumors, squamous cell carcinomas, mesothelioma, testicular seminoma, brain tumors and some types of vascular tumors as well as in some papillary thyroid tumors, suggesting the promising as a useful biomarker of cancer. Though PDPN does not contain known functional domains or enzymatic activities, it exerts the regulatory function via interacting with other ligands and binding partners, such as HSPA9, CD44, C-type lectin-like receptor-2 (CLEC-2), protein kinase A (PKA), cyclin-dependent kinase 5 (CDK5), etc. to control tumor cell migration, invasion and metastasis. Moreover, high levels of PDPN expression is associated with reduced survival and cancer aggression. In addition, PDPN is required to protect the barrier function of high endothelial venules (HEVs) during lymphocyte trafficking.

Fig.1 Podoplanin (PDPN) structure and targeting agents. (Krishnan, 2018)

Application of PDPN Membrane Protein in Literature

1. Yamada S., et al. Epitope mapping of anti-mouse podoplanin monoclonal antibody PMab-1. Biochem Biophys Rep. 2018, 15: 52-56. PubMed ID: 29998193
   
   

   The authors in this article use flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemical analyses to identify that the critical epitope of PMab-1 is Asp39 and Met41 of mPDPN, which can be applied to the production of more functional anti-mPDPN monoclonal antibodies.

2. Xie C., et al. Preparation of Anti-Human Podoplanin Monoclonal Antibody and its application in Immunohistochemical Diagnosis. Sci Rep. 2018, 8(1): 10162. PubMed ID: 29976954
   
   

   This article provides conclusive guidelines for the preparation of mAbs of Podoplanin and their applications in immunohistochemistry diagnosis.

3. Xie L., et al. Elevated expression of podoplanin and its clinicopathological, prognostic, and therapeutic values in squamous non-small cell lung cancer. Cancer Manag Res. 2018, 10: 1329-1340. PubMed ID: 29872344
   
   

   This article demonstrates a distinctively elevated expression of PDPN in squamous non-small cell lung cancer (SqNSCLC), which is significantly associated with worse clinicopathological features and poorer prognosis, indicating the potential of anti-PDPN targeted therapy for future SqNSCLC treatment.

4. Bond S.R., et al. Pannexin 3 is required for late stage bone growth but not for initiation of ossification in avian embryos. Dev Dyn. 2016, 245(9): 913-24. PubMed ID: 27295565
   
   

   This article demonstrates PANX3 hemichannels may be required to facilitate the transition of hypertrophic chondrocytes to osteoblasts, thereby achieving final bone size.

5. Suzuki-Inoue K. Roles of the CLEC-2-podoplanin interaction in tumor progression. Platelets. 2018, 4: 1-7. PubMed ID: 29863945
   
   

   This article indicates that anti-podoplanin and anti-CLEC-2 drugs are promising therapies for the prevention of tumor metastasis, progression, and tumor-related symptoms, which may result in longer survival in cancer patients.

PDPN Preparation Options

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Reference

1. Krishnan H, et al. (2018). Podoplanin: An emerging cancer biomarker and therapeutic target. Cancer Sci. 109: 1292-1299.

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