Inhibition of angiogenesis and suppression of colorectal cancer metastatic to the liver using the Sleeping Beauty Transposon System

Molecular Cancer

Research

Alice H Hsu¹  Lalitha R Belur²  R Scott McIvor²  Kelly M Podetz-Pedersen²  S Ramakrishnan³  Daniel A Saltzman⁴  Cathy S Carlson⁵  Brent S Sorenson⁵  Josh B Parker⁵ 

[1] Center for Genome Engineering, University of Minnesota, 55455, Minneapolis, MN, USA;Department of Genetics, Cell Biology and Development, University of Minnesota, 55455, Minneapolis, MN, USA;Center for Genome Engineering, University of Minnesota, 55455, Minneapolis, MN, USA;Gene Therapy Program, Institute of Human Genetics, University of Minnesota, 55455, Minneapolis, MN, USA;Department of Genetics, Cell Biology and Development, University of Minnesota, 55455, Minneapolis, MN, USA;Department of Pharmacology, University of Minnesota, 55455, Minneapolis, MN, USA;Department of Surgery, University of Minnesota, 55455, MN, USA;Department of Veterinary Population Medicine, University of Minnesota, 55108, St. Paul, MN, USA;

关键词: Sleep Beauty;    Sleep Beauty Transposase;    Antiangiogenic Gene Therapy;    CT26 Colon Carcinoma Cell;    Antiangiogenic Protein;   

DOI  :  10.1186/1476-4598-10-14

 received in 2010-04-19, accepted in 2011-02-10,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundMetastatic colon cancer is one of the leading causes of cancer-related death worldwide, with disease progression and metastatic spread being closely associated with angiogenesis. We investigated whether an antiangiogenic gene transfer approach using the Sleeping Beauty (SB) transposon system could be used to inhibit growth of colorectal tumors metastatic to the liver.ResultsLiver CT26 tumor-bearing mice were hydrodynamically injected with different doses of a plasmid containing a transposon encoding an angiostatin-endostatin fusion gene (Statin AE) along with varying amounts of SB transposase-encoding plasmid. Animals that were injected with a low dose (10 μg) of Statin AE transposon plasmid showed a significant decrease in tumor formation only when co-injected with SB transposase-encoding plasmid, while for animals injected with a higher dose (25 μg) of Statin AE transposon, co-injection of SB transposase-encoding plasmid did not significantly affect tumor load. For animals injected with 10 μg Statin AE transposon plasmid, the number of tumor nodules was inversely proportional to the amount of co-injected SB plasmid. Suppression of metastases was further evident in histological analyses, in which untreated animals showed higher levels of tumor cell proliferation and tumor vascularization than animals treated with low dose transposon plasmid.ConclusionThese results demonstrate that hepatic colorectal metastases can be reduced using antiangiogenic transposons, and provide evidence for the importance of the transposition process in mediating suppression of these tumors.

【 授权许可】

CC BY   
© Belur et al; licensee BioMed Central Ltd. 2011