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一种新型血小板反应蛋白-1变体作为犬乳腺肿瘤和骨肉瘤细胞潜在的诊断生物标志物和治疗靶点。

A novel thrombospondin-1 variant as a potential diagnostic biomarker and therapeutic target in canine mammary tumor and osteosarcoma cells.

作者信息

Hong Yukyung, Baik Heyeon, Lee Jeongmin, Oh Won Seok, Ryu Junsun, Baek Seung Joon

机构信息

College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea.

Korea Animal Medical Center, Cheongju 28651, Korea.

出版信息

J Vet Sci. 2025 Mar;26(2):e22. doi: 10.4142/jvs.24165.

DOI:10.4142/jvs.24165
PMID:40183909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11972944/
Abstract

IMPORTANCE

Thrombospondin-1 (TSP1) is a vital glycoprotein that plays a key role in critical biological functions, including cell migration, invasion, angiogenesis, and proliferation. Understanding the roles of its variants, particularly TSP1 variant (TSP1V), is critical for cancer biology and therapy.

OBJECTIVE

This study examined the expression of the transcriptional variant TSP1V, focusing on canine TSP1 sequences.

METHODS

The expression of canine TSP1 sequences was analyzed using a reverse transcription polymerase chain reaction (RT-PCR) to identify the wild-type () and novel canine transcripts (). The effects of damnacanthal and genistein, anticancer compounds, on the viability of canine mammary and osteosarcoma cell lines were assessed by modulating the expression ratios of to at the transcriptional level. RT-PCR analysis compared the relative and concentrations in normal and tumor canine mammary tissues.

RESULTS

Two were identified. Treatment with damnacanthal and genistein decreased cell proliferation in canine mammary and osteosarcoma cell lines, associated with changes in the to expression ratio. RT-PCR analysis revealed increased expression in normal tissues, while expression was elevated in tumor tissues.

CONCLUSIONS AND RELEVANCE

TSP1V may be a potential diagnostic biomarker and therapeutic target for mammary tumors and osteosarcoma in dogs. The differential expression of and in normal versus tumor tissues underscores the importance of TSPIV in cancer biology, expanding the understanding of its role beyond human thyroid cancer and laying the groundwork for future research in other cancers and species.

摘要

重要性

血小板反应蛋白-1(TSP1)是一种重要的糖蛋白,在包括细胞迁移、侵袭、血管生成和增殖等关键生物学功能中起关键作用。了解其变体,特别是TSP1变体(TSP1V)的作用,对癌症生物学和治疗至关重要。

目的

本研究检测转录变体TSP1V的表达,重点关注犬TSP1序列。

方法

使用逆转录聚合酶链反应(RT-PCR)分析犬TSP1序列的表达,以鉴定野生型()和新的犬转录本()。通过在转录水平调节与的表达比例,评估抗癌化合物金丝桃素和染料木黄酮对犬乳腺和骨肉瘤细胞系活力的影响。RT-PCR分析比较了正常和肿瘤犬乳腺组织中与的相对浓度。

结果

鉴定出两种。金丝桃素和染料木黄酮处理降低了犬乳腺和骨肉瘤细胞系中的细胞增殖,这与与表达比例的变化有关。RT-PCR分析显示正常组织中表达增加,而肿瘤组织中表达升高。

结论及意义

TSP1V可能是犬乳腺肿瘤和骨肉瘤的潜在诊断生物标志物和治疗靶点。与在正常组织和肿瘤组织中的差异表达强调了TSPIV在癌症生物学中的重要性,扩展了对其作用的理解,超越了人类甲状腺癌,并为未来其他癌症和物种的研究奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2daa/11972944/2ba82d67eb42/jvs-26-e22-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2daa/11972944/10b34798f162/jvs-26-e22-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2daa/11972944/de196e5cfc93/jvs-26-e22-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2daa/11972944/b2a7184924fe/jvs-26-e22-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2daa/11972944/2ba82d67eb42/jvs-26-e22-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2daa/11972944/10b34798f162/jvs-26-e22-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2daa/11972944/de196e5cfc93/jvs-26-e22-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2daa/11972944/b2a7184924fe/jvs-26-e22-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2daa/11972944/2ba82d67eb42/jvs-26-e22-g004.jpg

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本文引用的文献

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Oncogene. 2023 Jun;42(22):1832-1842. doi: 10.1038/s41388-023-02692-9. Epub 2023 Apr 13.
2
GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells.GDF15 通过介导乳腺癌细胞的 EMT 和干性促进放射抵抗。
Int J Mol Sci. 2022 Sep 18;23(18):10911. doi: 10.3390/ijms231810911.
3
PKHB1, a thrombospondin-1 peptide mimic, induces anti-tumor effect through immunogenic cell death induction in breast cancer cells.
PKHB1,一种血小板反应蛋白-1 肽模拟物,通过诱导乳腺癌细胞免疫原性细胞死亡发挥抗肿瘤作用。
Oncoimmunology. 2022 Apr 4;11(1):2054305. doi: 10.1080/2162402X.2022.2054305. eCollection 2022.
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Comparison of mucin-1 in human breast cancer and canine mammary gland tumor: a review study.人乳腺癌与犬乳腺肿瘤中粘蛋白-1的比较:一项综述研究。
Cancer Cell Int. 2022 Jan 9;22(1):14. doi: 10.1186/s12935-021-02398-6.
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