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Cancer Patient–Derived Circulating Microparticles Enhance Lung Metastasis in a Rat Model: Dual-Source CT, Cellular, and Molecular Studies

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Abstract

Purpose

This study aimed to test the hypothesis that lung cancer patient–derived circulating microparticles (LCC-MPs) enhance metastatic lung tumors in a rat model.

Procedures

The controls (n = 6) and LCC-MP-treated rats (n = 6) with N1S1-induced pulmonary metastatic hepatocellular carcinoma (HCC) underwent dual-source CT (DSCT) on days 10, 15, and 20. Cellular and molecular studies were performed subsequently.

Results

DSCT revealed slow progression of metastatic lung tumors in the controls. Compared with the controls, the LCC-MP-treated rats exhibited significantly more and larger metastatic tumors on days 15 and 20 on DSCT, enhanced angiogenesis with higher microvessel count (CD34+), more CXCR4+ and VEGF+ cells in immunohistofluorescence studies, and higher protein expression levels of eNOS, angiopoietin, vascular endothelial growth factor, and CD31 on western blotting (Mann–Whitney test, all P < 0.05).

Conclusions

LCC-MPs can elicit oncogenic stimulation and accelerate metastatic HCC growth in rat lung as demonstrated on DSCT and enhanced tumoral angiogenesis as confirmed in cellular and molecular studies.

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Authors and Affiliations

  1. Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung District, Kaohsiung, 833, Taiwan

    Sheung-Fat Ko, Jung-Hui Li, Chen-Chang Lee, Chung-Cheng Huang & Shu-Hang Ng

  2. Department of Cardiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan

    Hon-Kan Yip

  3. Department of Medical Researches, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan

    Yen-Yi Zhen & Chia-Chang Lee

  4. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan

    Chen-Chang Lee

  5. Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan

    Steve Leu

  6. Department of Biomedical Engineering, I-Shou University, Kaohsiung, 833, Taiwan

    Jui-Wei Lin

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  1. Sheung-Fat Ko
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  2. Hon-Kan Yip
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Corresponding author

Correspondence to Sheung-Fat Ko.

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Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This study was funded by the Chang Gung Medical Foundation, Taiwan (grant number CMRPG8C0271).

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Ko, SF., Yip, HK., Zhen, YY. et al. Cancer Patient–Derived Circulating Microparticles Enhance Lung Metastasis in a Rat Model: Dual-Source CT, Cellular, and Molecular Studies. Mol Imaging Biol 18, 490–499 (2016). https://doi.org/10.1007/s11307-015-0923-8

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  • DOI: https://doi.org/10.1007/s11307-015-0923-8

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