Aerosol Delivery of Small Hairpin Osteopontin Blocks Pulmonary Metastasis of Breast Cancer in Mice

• Type of Material: Article
• Authors: Kyeong-Nam Yu, Seoul National University; Arash Minai-Tehrani, Seoul National University; Seung-Hee Chang, Seoul National University; Soon-Kyung Hwang, Seoul National University; Seong-Ho Hong, Seoul National University; Ji-Eun Kim, Seoul National University; Ji-Young Shin, Seoul National University; Sung-Jin Park, Seoul National University; Ji-Hye Kim, Seoul National University; Jung-Taek Kwon, Seoul National University; Hu-Lin Jiang, Seoul National University; Bitna Kang, Seoul National University; Duyeol Kim, Seoul National University; Chan-Hee Chae, Seoul National University; Kee-Ho Lee, Korea Institute of Radiological & Medical Sciences; Tae-Jong Yoon, CHA University; George Beck Jr, Emory University; Myung-Haing Cho, Seoul National University
• Language: English
• Date: 2010-12-22
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: Yu et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0015623
• Title of Journal or Parent Work: PLOS ONE
• Volume: 5
• Issue: 12
• Start Page: e15623
• End Page: e15623
• Grant/Funding Information: This work was supported by the National Research Foundation (NRF-2010-0000784), Ministry of Education, Science and Technology (MEST), Korea. Kee-Ho Lee was supported by the 21C Frontier Functional Human Genome Project (FG03-0601-003-1-0-0) and by the National Nuclear R&D Program of the Ministry of Science and Technology. George R. Beck Jr was supported in part by grants from NIH/NIAMS (AR056090) and NIH/NCI (CA136059). Myung-Haing Cho was also partially supported by the Research Institute for Veterinary Science, Seoul National University. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: ENDOTHELIAL GROWTH-FACTOR; LIVER METASTASIS; LUNG; RNA; TUMOR PROGRESSION; Science & Technology; VECTORS; EXPRESSION; Multidisciplinary Sciences; Science & Technology - Other Topics; GENE-THERAPY; ANGIOGENESIS; PROTEIN
• Research Categories: Biology, Genetics; Health Sciences, Oncology

Abstract

Background: Metastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed. Methodology/Principal Finding: Aerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model. Conclusion/Significance: Aerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.© 2010 Yu et al.