Podoplanin (PDPN), a transmembrane receptor also known as E11 antigen and gp38, is involved in multiple physiological and pathological processes. It plays roles in cell motility, invasion, tumor metastasis, blood vessel formation, and platelet activation. PDPN interacts with C-type lectin-like receptor-2 (CLEC-2) in relevant pathways [3,7,8].

In cancer research, knockdown of PDPN radiosensitized glioma cell lines and glioma-stem-like cells (GSCs), improving overall survival in an intracranial xenograft mouse model, indicating its role in radiation resistance and tumor aggressiveness in gliomas [2]. In oral squamous cell carcinoma (OSCC), PDPN + cancer-associated fibroblasts (CAFs) promoted OSCC progression by transferring exosomal lncRNA FTX to inhibit ferroptosis in OSCC cells [1]. In gastric cancer, PDPN + CAFs enhanced angiogenesis via AKT/NF-κB activation and the CCL2-ACKR1 axis [4]. In breast cancer, PDPN-expressing macrophages promoted lymphangiogenesis and lymphoinvasion [5]. In thyroid carcinoma cells, PDPN affected invasiveness by inducing ezrin, radixin and moesin (E/R/M) phosphorylation in association with matrix metalloproteinases [6]. In glioblastoma multiforme (GBM), PDPN promoted tumor metastasis [7]. In canine malignant melanoma, silencing of Pdpn induced apoptosis and cell cycle arrest [9].

In summary, PDPN is crucial in processes like cell proliferation, tumor-related angiogenesis, metastasis, and radiation resistance. The use of gene-knockdown models, similar to gene knockout in concept, has revealed its role in various cancer-related disease conditions, providing potential therapeutic targets for these cancers.

References:

1. Li, Yaoyin, Ma, Zeyi, Li, Weiyu, Cheng, Bin, Xia, Juan. 2023. PDPN+ CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX. In Cell death & disease, 14, 759. doi:10.1038/s41419-023-06280-3. https://pubmed.ncbi.nlm.nih.gov/37993428/

2. Modrek, Aram S, Eskilsson, Eskil, Ezhilarasan, Ravesanker, Aldape, Kenneth D, Sulman, Erik P. 2022. PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells. In Frontiers in oncology, 12, 941657. doi:10.3389/fonc.2022.941657. https://pubmed.ncbi.nlm.nih.gov/36059614/

3. Gao, Yi, Qin, Lihong, Yang, Yuwei, Zhang, Guoliang, Zhao, Zhihui. 2017. PDPN gene promotes the proliferation of immature Bovine Sertoli cells in vitro. In Animal reproduction science, 179, 35-43. doi:10.1016/j.anireprosci.2017.01.014. https://pubmed.ncbi.nlm.nih.gov/28233584/

4. Zhao, Zhenxiong, Sun, Hui, Liu, Yingxue, Sheng, Weiqi, Xu, Mi-Die. 2025. PDPN+ cancer-associated fibroblasts enhance gastric cancer angiogenesis via AKT/NF-κB activation and the CCL2-ACKR1 axis. In MedComm, 6, e70037. doi:10.1002/mco2.70037. https://pubmed.ncbi.nlm.nih.gov/39764562/

5. Bieniasz-Krzywiec, Paweł, Martín-Pérez, Rosa, Ehling, Manuel, Van Ginderachter, Jo A, Mazzone, Massimiliano. 2019. Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer. In Cell metabolism, 30, 917-936.e10. doi:10.1016/j.cmet.2019.07.015. https://pubmed.ncbi.nlm.nih.gov/31447322/

6. Sikorska, Justyna, Gaweł, Damian, Domek, Hanna, Rudzińska, Magdalena, Czarnocka, Barbara. 2019. Podoplanin (PDPN) affects the invasiveness of thyroid carcinoma cells by inducing ezrin, radixin and moesin (E/R/M) phosphorylation in association with matrix metalloproteinases. In BMC cancer, 19, 85. doi:10.1186/s12885-018-5239-z. https://pubmed.ncbi.nlm.nih.gov/30654768/

7. Sharma, Bharti, Agriantonis, George, Shafaee, Zahra, Ghanta, Hima, Whittington, Jennifer. 2024. Role of Podoplanin (PDPN) in Advancing the Progression and Metastasis of Glioblastoma Multiforme (GBM). In Cancers, 16, . doi:10.3390/cancers16234051. https://pubmed.ncbi.nlm.nih.gov/39682237/

8. Nara, Rikuto, Notoh, Hinako, Sasaki, Tomoyuki, Matsushita, Tadashi, Tamura, Shogo. 2024. PDPN/CLEC-2 axis modulates megakaryocyte subtypes in a hematopoietic stem cell-regulating megakaryocyte-dominant manner. In Thrombosis research, 245, 109230. doi:10.1016/j.thromres.2024.109230. https://pubmed.ncbi.nlm.nih.gov/39615442/

9. Shinada, Masahiro, Kato, Daiki, Kamoto, Satoshi, Kato, Yukinari, Nakagawa, Takayuki. 2020. PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma. In Cells, 9, . doi:10.3390/cells9051136. https://pubmed.ncbi.nlm.nih.gov/32380790/