Olfactomedin 4 suppresses tumor growth and metastasis of mouse melanoma cells through downregulation of integrin and MMP genes |
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Authors: | Key Sun Park Kee Kwang Kim Zheng-Hao Piao Mi Kyung Kim Hyun Jean Lee Yong Chan Kim Ki Sung Lee Jeung-Hoon Lee Kyoon Eon Kim |
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Institution: | 1. Department of Biochemistry, Chungnam National University, Daejeon, 305-764, Korea 2. Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA 3. Department of Basic Medical Sciences, Hangzhou Normal University School of Medicine, Xiasha Higher Education Zone, Hangzhou, China 4. Department of Medicine (MED), USUHS Building A, Bethesda, MD, 20814, USA 5. Department of Biology and Medicinal Science, College of Sciences and Technology, Pai Chai University, Daejeon, 302-735, Korea 6. Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, 301-747, Korea
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Abstract: | Olfactomedin 4 (OLFM4) is highly expressed in gastrointestinal cancers and has an anti-apoptotic function. The roles of OLFM4 in tumor growth and metastasis and how it functions in these processes remain elusive. We investigated the function of OLFM4 in tumor growth and metastasis using B16F10 mouse melanoma cells as an experimental system. Our results showed that OLFM4 had no positive effect on cell viability or cell cycle progression in B16F10 cells. However, it significantly suppressed the tumorigenicity of B16F10 cells, i.e., intradermal primary tumor growth and lung metastasis. OLFM4 also suppressed the migration and invasion of B16F10 cells in vitro. For further insight into the mechanisms underlying OLFM4-mediated suppression of tumor progression, we examined the effect of OLFM4 on the expression of integrin and matrix metalloproteinase (MMP), both of which are involved in tumor progression. Overexpression of OLFM4 clearly reduced the expression levels of integrin α1, integrin α4, integrin α5, integrin α6, and MMP9. Moreover, forced expression of MMP9 attenuated the inhibitory activity of OLFM4 on migration and invasiveness. Our findings provide the experimental evidence that OLFM4 may function as a tumor suppressor and an anti-metastatic gene during tumor progression. |
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Keywords: | B16F10 cells cancer metastasis OLFM4 tumor growth |
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