title: Human lung cancer-derived microparticles enhanced angiogenesis and growth of hepatoma cells in rodent lung parenchyma.
abstract: This study tested the hypothesis that human lung cancer-derived microparticles (LcD-MPs) played an important role in tumor angiogenesis and growth. Fischer 344 rats (F344, n=18) were equally categorized into group 1 [Sham Control (3.0 mL normal saline intravenous injection (IV))], group 2 [hepatoma cell line (2.0 x 10(6) cells, IV)], and group 3 [hepatoma cell line + LcD-MPs (3.0 x 10(6), IV)]. Animals were euthanized by day 28 after hepatoma cells transfusion. Our result showed that the gross pathology confirmed growth of hepatoma cell line in lung parenchyma. The size and weight of the lungs were significantly increased in group 2 and further elevated in group 3 than in group 1 (all p<0.001). Histopathological analysis demonstrated that the lung crowded score and number of small vessel exhibited an identical pattern, whereas the number of alveolar sacs showed an opposite pattern compared to that of total lung weight among the three groups (all p<0.0001). The cellular expressions of CD34(+), CXCR4(+), c-Kit(+), CK19(+), VEGF(+) and vimentin+ cells in lung parenchyma exhibited an identical pattern compared to those of total lung weight among all groups (all p<0.001). The protein expressions of apoptotic (Bax, cleaved caspase-3 and c-PARP), fibrotic (Smad3, TGF-β), and tumor suppression (PTEN) biomarkers showed an identical pattern, whereas that of anti-apoptotic (Bcl-2) and anti-fibrotic (Smad1/5, BMP-2) biomarkers were displayed an opposite pattern compared to that of total lung weight among all groups (all p<0.001). The MPs could enhance angiogenesis and accelerated hepatoma cell growth in rodent lung parenchyma.
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Sheung-Fat
authors.initials: SF
authors.lastname: Ko
authors.affiliation: Department of Anatomy, Chang Gung University Taoyuan 33302, Taiwan.
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Hsu
authors.affiliation: Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Sung
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Meng-Shen TongYen-Yi
authors.initials: MS
authors.lastname: Zhen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Tien-Hung
authors.initials: TH
authors.lastname: Huang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Sheng-Yi
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Gour-Shenq
authors.initials: GS
authors.lastname: Kao
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Hong-Hwa
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung 83301, Taiwan.
authors.forename: Chia-Lo
authors.initials: CL
authors.lastname: Chang
authors.affiliation: Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students Kaohsiung 82445, Taiwan.
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University Kaohsiung 80424, Taiwan.
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung 83301, Taiwan; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan; Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial HospitalKaohsiung 83301, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical UniversityTaichung 40402, Taiwan; Department of Nursing, Asia UniversityTaichung 41354, Taiwan.
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
keywords: Lung cancer-derived microparticles; angiogenesis; lung parenchyma; tumor growth hepatocellular carcinoma