首页|Exosomes derived from pulmonary metastatic sites enhance osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS

Exosomes derived from pulmonary metastatic sites enhance osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS

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Osteosarcoma,a prevalent primary malignant bone tumor,often presents with lung metasta-ses,severely impacting patient survival rates.Extracellular vesicles,particularly exosomes,play a pivotal role in the formation and progression of osteosarcoma-related pulmonary lesions.However,the commu-nication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure,with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely unknown.This study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor site.This transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate(MARCKS)expression.Addressing this phenomenon,in this study we employ cationic bovine serum albumin(CBSA)to form nanoparticles(CBSA-anta-194/215)via electrostatic interaction with antagomir-miR-194/215.These nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles(anta-194/215@Exo)targeting osteosarcoma lung metastatic sites.Intervention with bioengineered exosome mimetics(anta-194/215@Exo)not only impedes osteosarcoma progression but also significantly pro-longs the lifespan of tumor-bearing mice.These findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS,making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.

Lung-bone transmissionmiR-194/215 clusterExosomeLung metastasisEpithelial-mesenchymal transitionVasculogenic mimicryBioengineered exosome mimeticsOsteosarcoma

Pei Yu、Yubao Han、Lulu Meng、Yanyuan Tian、Zhiwei Jin、Jun Luo、Chao Han、Wenjun Xu、Lingyi Kong、Chao Zhang

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State Key Laboratory of Natural Medicines,Jiangsu Key Laboratory of Bioactive Natural Product Research,School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China

国家自然科学基金国家自然科学基金国家自然科学基金Jiangsu Provincial Excellent Postdoctoral Program,China

8227407382304713818729862022ZB291

2024

10.1016/j.apsb.2024.01.016

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(5)
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