Watanabe Masataka, Mukudai Yoshiki, Kindaichi Nodoka, Nara Maki, Yamada Konomi, Abe Yuzo, Houri Asami, Shimane Toshikazu, Shirota Tatsuo
Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan.
Biomedicines. 2024 Nov 28;12(12):2725. doi: 10.3390/biomedicines12122725.
: The tumor protein D52 (TPD52) family includes TPD52, TPD53, TPD54, and TPD55. The balance between TPD52 and TPD54 expression plays an important role in high-malignant oral squamous cell carcinoma (OSCC) cells. However, the relationship between TPD53 and OSCC cells (particularly low-malignant OSCC cells) remains unclear. In the present study, we investigated the role of TPD53 in the malignant transformation of low-malignant OSCC cells. : Temporal changes in the expression of TPD52 family members at the protein and mRNA levels in OSCC cells and normal human epidermal keratinocytes (NHEK) were examined. : The mRNA expression of increased in HSC-3 and HSC-4 cells in a time-dependent manner. Similar results for protein expression were observed. The effects of TPD53 on anchorage-dependent and anchorage-independent proliferation, cell cycle, invasion and migration, epithelial-mesenchymal transition (EMT), and matrix metalloproteinase (MMP) activities in HSC-3 and HSC-4 cells were assayed. Finally, using the HSC-3-xenograft-nude-mice model, these effects were examined in vivo. Overexpression of increased cell viability and the percentage of cells in the S phase. Furthermore, overexpression of increased cell invasion, migration, and MMP activities, regardless of its effect on EMT. Notably, these effects were more pronounced in HSC-3 than in HSC-4 cells. Overexpression of enhanced tumor formation and growth in mouse xenografts, corroborating the results of in vitro experiments. : The present study revealed novel and important functions of TPD53 in the proliferation and invasion of low-malignant OSCC cells.
肿瘤蛋白D52(TPD52)家族包括TPD52、TPD53、TPD54和TPD55。TPD52和TPD54表达之间的平衡在高恶性口腔鳞状细胞癌(OSCC)细胞中起重要作用。然而,TPD53与OSCC细胞(特别是低恶性OSCC细胞)之间的关系仍不清楚。在本研究中,我们调查了TPD53在低恶性OSCC细胞恶性转化中的作用。:检测了OSCC细胞和正常人表皮角质形成细胞(NHEK)中TPD52家族成员在蛋白质和mRNA水平的表达随时间的变化。:HSC-3和HSC-4细胞中 的mRNA表达呈时间依赖性增加。蛋白质表达也观察到类似结果。检测了TPD53对HSC-3和HSC-4细胞中锚定依赖性和非锚定依赖性增殖、细胞周期、侵袭和迁移、上皮-间质转化(EMT)以及基质金属蛋白酶(MMP)活性的影响。最后,使用HSC-3异种移植裸鼠模型在体内检测了这些影响。 的过表达增加了细胞活力和S期细胞百分比。此外, 的过表达增加了细胞侵袭、迁移和MMP活性,无论其对EMT的影响如何。值得注意的是,这些影响在HSC-3细胞中比在HSC-4细胞中更明显。 的过表达增强了小鼠异种移植瘤的形成和生长,证实了体外实验的结果。:本研究揭示了TPD53在低恶性OSCC细胞增殖和侵袭中的新的重要功能。