PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma

PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma
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DOI：
10.3390/cells9051136
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发表时间：
2020-05-01
期刊：
CELLS
影响因子：
6
通讯作者：
Nakagawa, Takayuki
Nakagawa, Takayuki
中科院分区：
生物学2区
文献类型：
--
作者：
Shinada, Masahiro;Kato, Daiki;Nakagawa, Takayuki

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Podoplanin（PDPN）是一种小的跨膜粘蛋白样糖蛋白，异位表达。还已知它与某些类型的人类肿瘤中肿瘤恶性程度的几个方面有关，包括侵袭、转移和癌症干性。然而，关于犬PDPN（dPDPN）在犬肿瘤中的表达的报道很少，并且dPDPN与肿瘤恶性程度之间的关系尚未阐明。我们发现18种犬肿瘤中有11种表达dPDPN。此外，80%的犬恶性黑色素瘤（MM）、鳞状细胞癌和脑膜瘤表达dPDPN。此外，dPDPN的表达密度与Ki 67增殖标志物的表达呈正相关。siRNA沉默dPDPN导致犬MM细胞系中细胞迁移、侵袭、干细胞样特征和细胞活力的抑制。细胞活力的抑制是通过诱导细胞凋亡和G2/M期细胞阻滞引起的。总之，这项研究表明，dPDPN在各种类型的犬肿瘤中表达，并且dPDPN沉默通过细胞凋亡和细胞周期阻滞抑制细胞活力，从而为PDPN在肿瘤进展中提供了新的生物学作用。
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.