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sCLU 作为骨肉瘤的预后生物标志物和治疗靶点。

sCLU as prognostic biomarker and therapeutic target in osteosarcoma.

机构信息

a Department of Spine Surgery , The Affiliated Hospital of Qingdao University , Qingdao , Shandong , China.

b Department of Spine Surgery , The 107 Hospital of the People's Liberation Army , Yantai , Shandong , China.

出版信息

Bioengineered. 2019 Dec;10(1):229-239. doi: 10.1080/21655979.2019.1621136.

DOI:10.1080/21655979.2019.1621136
PMID:31117872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6592366/
Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor. Secretory apolipoprotein J/clusterin (sCLU) is overexpressed in many cancers; however, its role in OS has not been previously investigated. The objectives of this study were to address this question and also to assess the clinical value of sCLU as a prognostic biomarker and therapeutic target by comparing sCLU expression in human OS (n = 106), normal bone (n = 16), fibrous dysplasia (n = 9), and ossifying myositis (n = 11) tissues and by evaluating the effect of sCLU silencing on OS growth, invasion, and chemosensitivity in vitro and in vivo. We found that sCLU was highly expressed in OS tissue specimens, which was positively correlated with metastatic disease and negatively correlated with response to chemotherapy. knockdown in KHOS cells inhibited proliferation and invasion and increased apoptosis as well as sensitivity to the chemotherapy drug gemcitabine (Gem). In a mouse xenograft model, sCLU depletion suppressed lung metastasis and enhanced the effects of Gem, thereby slowing KHOS tumor growth. These results indicate that sCLU overexpression is a biomarker for malignant transformation of OS and that therapeutic strategies targeting sCLU may be an effective treatment for OS. ● Secretory apolipoprotein J/clusterin (sCLU) is overexpressed in osteosarcoma (OS). ● sCLU overexpression is associated with metastasis and chemoresistance. ● Silencing sCLU inhibits metastasis and enhances chemosensitivity in OS cells. sCLU is a biomarker for metastatic OS and a potential therapeutic target.

摘要

骨肉瘤（OS）是最常见的原发性恶性骨肿瘤。分泌载脂蛋白 J/簇蛋白（sCLU）在许多癌症中过度表达；然而，其在 OS 中的作用尚未被研究过。本研究的目的是解决这个问题，并通过比较 sCLU 在人骨肉瘤（n=106）、正常骨（n=16）、纤维结构不良（n=9）和骨化性肌炎（n=11）组织中的表达，评估 sCLU 作为预后生物标志物和治疗靶点的临床价值，并评估 sCLU 沉默对 OS 体外和体内生长、侵袭和化学敏感性的影响。我们发现 sCLU 在 OS 组织标本中高度表达，与转移性疾病呈正相关，与化疗反应呈负相关。在 KHOS 细胞中敲低 sCLU 抑制增殖和侵袭，增加细胞凋亡和对化疗药物吉西他滨（Gem）的敏感性。在小鼠异种移植模型中，sCLU 耗竭抑制肺转移并增强 Gem 的作用，从而减缓 KHOS 肿瘤生长。这些结果表明 sCLU 过表达是 OS 恶性转化的一个生物标志物，靶向 sCLU 的治疗策略可能是 OS 的有效治疗方法。 ● 分泌载脂蛋白 J/簇蛋白（sCLU）在骨肉瘤（OS）中过度表达。 ● sCLU 过表达与转移和化疗耐药有关。 ● 沉默 sCLU 抑制 OS 细胞的转移并增强其化学敏感性。 sCLU 是转移性 OS 的生物标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/0e413a893f1d/kbie-10-01-1621136-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/5e157ca55736/kbie-10-01-1621136-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/6103e4108ceb/kbie-10-01-1621136-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/b60aa3944893/kbie-10-01-1621136-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/15a74ba9ffc4/kbie-10-01-1621136-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/0e413a893f1d/kbie-10-01-1621136-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/5e157ca55736/kbie-10-01-1621136-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/6103e4108ceb/kbie-10-01-1621136-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/b60aa3944893/kbie-10-01-1621136-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/15a74ba9ffc4/kbie-10-01-1621136-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e344/6592366/0e413a893f1d/kbie-10-01-1621136-g005.jpg

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