Theranostics 2015; 5(7):724-732. doi:10.7150/thno.10734

Research Paper

Longitudinal Tracing of Spontaneous Regression and Anti-angiogenic Response of Individual Microadenomas during Colon Tumorigenesis

Jin Woo Choi1,2,3✉, Pilhan Kim4, Jun Ki Kim5, Yi Rang Kim4,6,7, Dai Fukumura8, Seok Hyun Yun1,4✉

1. Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, 40 Blossom St., Boston, MA 02114, USA
2. Department of Pharmacology and Dental Research Institute, School of Dentistry / Department of Smart Life-Care Convergence Graduate School, Wonkwang University, Iksan, Chonbuk 570-749, Korea
3. Advanced Institute of Convergence Technology, Seoul National University, Suwon Gyeonggi-do 443-270, Korea
4. Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejeon 305-701, Korea
5. Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center and University of Ulsan College of Medicine, Seoul 138-736, Korea
6. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejeon 305-701, Korea
7. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
8. Edwin L. Steele Lab of Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA

Abstract

Angiogenesis is essential for the progression of cancer, but its involvement in the initial phase of colon tumorigenesis is not well understood. Using intravital endomicroscopy, we visualized the natural history of early pre-tumorous lesions and adenomas in the colon of conditional Apc-knockout and Apc/Kras double mutant mouse models. Early lesions emerged about 4 weeks after the onset of somatic mutations, accompanying vascular dilation when the size of lesions reached about 200 μm, but most lesions regressed spontaneously and cleared within 10 weeks after their emergence. Anti-angiogenic treatments with vascular endothelial growth factor receptor (VEGFR) antagonists reduced the size of the early lesions and the number of polyps. We found surprisingly that anti-angiogenic treatments delayed the natural clearance of transient lesions by up to several weeks in both genetic models. The results represent the previously unexpected role of early angiogenesis on the spontaneous regression of early-stage colon tumors.

Keywords: Angiogenesis, tumorigenesis, colon tumor

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How to cite this article:
Choi JW, Kim P, Kim JK, Kim YR, Fukumura D, Yun SH. Longitudinal Tracing of Spontaneous Regression and Anti-angiogenic Response of Individual Microadenomas during Colon Tumorigenesis. Theranostics 2015; 5(7):724-732. doi:10.7150/thno.10734. Available from http://www.thno.org/v05p0724.htm