Podoplanin Promotes Cell Proliferation, Survival, and Migration of Canine Non-tonsillar Squamous Cell Carcinoma

Overview

Journal J Vet Med Sci

Specialty Veterinary Medicine

Date 2023 Aug 6

PMID 37544715

Authors

Masahiro Shinada

Daiki Kato

Masaya Tsuboi

Namiko Ikeda

Susumu Aoki

Takaaki Iguchi

Toshio Li

Yuka Kodera

Ryosuke Ota

Shoma Koseki

Hayato Shibahara

Yosuke Takahashi

Yuko Hashimoto

James K Chambers

Kazuyuki Uchida

Shunsuke Noguchi

Yukinari Kato

Ryohei Nishimura

Takayuki Nakagawa

Affiliations

Soon will be listed here.

Abstract

Podoplanin (PDPN) is a prognostic factor and is involved in several mechanisms of tumor progression in human squamous cell carcinoma (SCC). Canine non-tonsillar SCC (NTSCC) is a common oral tumor in dogs and has a highly invasive characteristic. In this study, we investigated the function of PDPN in canine NTSCC. In canine NTSCC clinical samples, PDPN overexpression was observed in 80% of dogs with NTSCC, and PDPN expression was related to ki67 expression. In PDPN knocked-out canine NTSCC cells, cell proliferation, cancer stemness, and migration were suppressed. As the mechanism of PDPN-mediated cell proliferation, PDPN knocked-out induced apoptosis and G2/M cell cycle arrest in canine NTSCC cells. These findings suggest that PDPN promotes tumor malignancies and may be a novel biomarker and therapeutic target for canine NTSCC.

Citing Articles

Podoplanin depletion in tonsil-derived mesenchymal stem cells induces cellular senescence via regulation of the p16/Rb pathway.

Kim H, Kim H Cell Commun Signal. 2024; 22(1):323.

PMID: 38867259 PMC: 11167904. DOI: 10.1186/s12964-024-01705-8.

References

Martin-Villar E, Borda-dAgua B, Carrasco-Ramirez P, Renart J, Parsons M, Quintanilla M . Podoplanin mediates ECM degradation by squamous carcinoma cells through control of invadopodia stability. Oncogene. 2014; 34(34):4531-44. PMC: 4430312. DOI: 10.1038/onc.2014.388. View

Miyashita T, Higuchi Y, Kojima M, Ochiai A, Ishii G . Single cell time-lapse analysis reveals that podoplanin enhances cell survival and colony formation capacity of squamous cell carcinoma cells. Sci Rep. 2017; 7:39971. PMC: 5216406. DOI: 10.1038/srep39971. View

Schwab M, Lohr S, Schneider J, Kaiser M, Krunic D, Helbig D . Podoplanin is required for tumor cell invasion in cutaneous squamous cell carcinoma. Exp Dermatol. 2021; 30(11):1619-1630. DOI: 10.1111/exd.14344. View

Wu Y, Liu Q, Yan X, Kato Y, Tanaka M, Inokuchi S . Podoplanin-mediated TGF-β-induced epithelial-mesenchymal transition and its correlation with bHLH transcription factor DEC in TE-11 cells. Int J Oncol. 2016; 48(6):2310-20. PMC: 4863730. DOI: 10.3892/ijo.2016.3445. View

Grier C, Mayer M . Radiation therapy of canine nontonsillar squamous cell carcinoma. Can Vet J. 2007; 48(11):1189-91. PMC: 2034434. View

Canueto J, Cardenoso-Alvarez E, Cosano-Quero A, Santos-Briz A, Fernandez-Lopez E, Perez-Losada J . The expression of podoplanin is associated with poor outcome in cutaneous squamous cell carcinoma. J Cutan Pathol. 2016; 44(2):144-151. DOI: 10.1111/cup.12859. View

Maruyama Y, Maruyama K, Kato Y, Kajiya K, Moritoh S, Yamamoto K . The effect of podoplanin inhibition on lymphangiogenesis under pathological conditions. Invest Ophthalmol Vis Sci. 2014; 55(8):4813-22. DOI: 10.1167/iovs.13-13711. View

Shinada M, Kato D, Kamoto S, Yoshimoto S, Tsuboi M, Yoshitake R . PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma. Cells. 2020; 9(5). PMC: 7290317. DOI: 10.3390/cells9051136. View

Hsu S, Lin P, Chou C, Lee W . Progesterone up-regulates p27 through an increased binding of the progesterone receptor-A-p53 protein complex onto the non-canonical p53 binding motif in HUVEC. J Steroid Biochem Mol Biol. 2018; 185:163-171. DOI: 10.1016/j.jsbmb.2018.08.011. View

10.

Krishnan H, Rayes J, Miyashita T, Ishii G, Retzbach E, Sheehan S . Podoplanin: An emerging cancer biomarker and therapeutic target. Cancer Sci. 2018; 109(5):1292-1299. PMC: 5980289. DOI: 10.1111/cas.13580. View

11.

Quintanilla M, Montero-Montero L, Renart J, Martin-Villar E . Podoplanin in Inflammation and Cancer. Int J Mol Sci. 2019; 20(3). PMC: 6386838. DOI: 10.3390/ijms20030707. View

12.

Khanna K, Lavin M, Jackson S, MULHERN T . ATM, a central controller of cellular responses to DNA damage. Cell Death Differ. 2001; 8(11):1052-65. DOI: 10.1038/sj.cdd.4400874. View

13.

Xia Z, Meng F, Fang Y, Wu X, Zhang C, Liu Y . Inhibition of NF-κB signaling pathway induces apoptosis and suppresses proliferation and angiogenesis of human fibroblast-like synovial cells in rheumatoid arthritis. Medicine (Baltimore). 2018; 97(23):e10920. PMC: 5999456. DOI: 10.1097/MD.0000000000010920. View

14.

Yao J, Duan L, Fan M, Wu X . NF-kappaB signaling pathway is involved in growth inhibition, G2/M arrest and apoptosis induced by Trichostatin A in human tongue carcinoma cells. Pharmacol Res. 2006; 54(6):406-13. DOI: 10.1016/j.phrs.2006.08.003. View

15.

Bergin I, Smedley R, Esplin D, Spangler W, Kiupel M . Prognostic evaluation of Ki67 threshold value in canine oral melanoma. Vet Pathol. 2010; 48(1):41-53. DOI: 10.1177/0300985810388947. View

16.

Awasthi P, Foiani M, Kumar A . ATM and ATR signaling at a glance. J Cell Sci. 2015; 128(23):4255-62. DOI: 10.1242/jcs.169730. View

17.

Kamoto S, Shinada M, Kato D, Tsuboi M, Yoshimoto S, Yoshitake R . Expression of podoplanin in various types of feline tumor tissues. J Vet Med Sci. 2021; 83(11):1795-1799. PMC: 8636872. DOI: 10.1292/jvms.20-0608. View

18.

Mosca A, Gibson D, Mason S, Dobson J, Giuliano A . A possible role of coarse fractionated radiotherapy in the management of gingival squamous cell carcinoma in dogs: A retrospective study of 21 cases from two referral centers in the UK. J Vet Med Sci. 2021; 83(3):447-455. PMC: 8025409. DOI: 10.1292/jvms.20-0191. View

19.

Acton S, Farrugia A, Astarita J, Mourao-Sa D, Jenkins R, Nye E . Dendritic cells control fibroblastic reticular network tension and lymph node expansion. Nature. 2014; 514(7523):498-502. PMC: 4235005. DOI: 10.1038/nature13814. View

20.

Boria P, Murry D, Bennett P, Glickman N, Snyder P, Merkel B . Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs. J Am Vet Med Assoc. 2004; 224(3):388-94. DOI: 10.2460/javma.2004.224.388. View