PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma
1
Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
2
Veterinary Medical Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
3
Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
4
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
5
New Industry Creation Hatchery Center, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
*
Author to whom correspondence should be addressed.
Cells 2020, 9(5), 1136; https://doi.org/10.3390/cells9051136
Received: 25 March 2020 / Revised: 2 May 2020 / Accepted: 4 May 2020 / Published: 5 May 2020
(This article belongs to the Special Issue Structure and Function of Podoplanin (PDPN) in Disease)
Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed. It is also known to be linked with several aspects of tumor malignancy in some types of human tumors, including invasion, metastasis, and cancer stemness. However, there are few reports on the expression of dog PDPN (dPDPN) in canine tumors, and the association between dPDPN and tumor malignancy has not been elucidated. We identified that 11 out of 18 types of canine tumors expressed dPDPN. Furthermore, 80% of canine malignant melanoma (MM), squamous cell carcinoma, and meningioma expressed dPDPN. Moreover, the expression density of dPDPN was positively associated with the expression of the Ki67 proliferation marker. The silencing of dPDPN by siRNAs resulted in the suppression of cell migration, invasion, stem cell-like characteristics, and cell viability in canine MM cell lines. The suppression of cell viability was caused by the induction of apoptosis and G2/M phase cell cycle arrest. Overall, this study demonstrates that dPDPN is expressed in various types of canine tumors and that dPDPN silencing suppresses cell viability through apoptosis and cell cycle arrest, thus providing a novel biological role for PDPN in tumor progression.
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Keywords:
podoplanin; cancer; Ki67; melanoma; squamous cell carcinoma; apoptosis; cell cycle
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Shinada, M.; Kato, D.; Kamoto, S.; Yoshimoto, S.; Tsuboi, M.; Yoshitake, R.; Eto, S.; Ikeda, N.; Saeki, K.; Hashimoto, Y.; Takahashi, Y.; Chambers, J.; Uchida, K.; Kaneko, M.K.; Fujita, N.; Nishimura, R.; Kato, Y.; Nakagawa, T. 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, 1136.
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