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

Mol Imaging Biol. 2016 Aug;18(4):490-9. doi: 10.1007/s11307-015-0923-8.

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.

Keywords: Angiogenesis; Animals; Computed tomography; Hepatocellular carcinoma; Liver cancer; Lung cancer; Lung metastasis; Microparticles; Molecular biology; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell-Derived Microparticles / metabolism*
  • Disease Models, Animal
  • Fluorescence
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / secondary*
  • Male
  • Molecular Imaging*
  • Radiographic Image Enhancement
  • Rats, Inbred F344
  • Tomography, X-Ray Computed*