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Mol. Cells 2012; 34(6): 555-561

Published online December 31, 2012

https://doi.org/10.1007/s10059-012-0251-7

© The Korean Society for Molecular and Cellular Biology

Olfactomedin 4 Suppresses Tumor Growth and Metastasis of Mouse Melanoma Cells through Downregulation of Integrin and MMP Genes

Key Sun Park1,7, Kee Kwang Kim1,2,7, Zheng-Hao Piao1,3, Mi Kyung Kim1, Hyun Jean Lee1, Yong Chan Kim1,4, Ki Sung Lee5, Jeung-Hoon Lee6, and Kyoon Eon Kim1,*

1Department of Biochemistry, Chungnam National University, Daejeon 305-764, Korea, 2Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA, 3Department of Basic Medical Sciences, Hangzhou Normal University School of Medicine, Xiasha Higher Education Zone, Hangzhou, China, 4Department of Medicine (MED), USUHS Building A, Bethesda, MD 20814, USA, 5Department of Biology and Medicinal Science, College of Sciences and Technology, Pai Chai University, Daejeon 302-735, Korea, 6Department of Dermatology, College of Medicine, Chungnam National University, Daejeon 301-747, Korea, 7These authors contributed equally to this work.

Correspondence to : *Correspondence: kyoonkim@cnu.ac.kr

Received: September 20, 2012; Accepted: October 10, 2012

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.

Keywords B16F10 cells, cancer, metastasis, OLFM4, tumor growth

Article

Research Article

Mol. Cells 2012; 34(6): 555-561

Published online December 31, 2012 https://doi.org/10.1007/s10059-012-0251-7

Copyright © The Korean Society for Molecular and Cellular Biology.

Olfactomedin 4 Suppresses Tumor Growth and Metastasis of Mouse Melanoma Cells through Downregulation of Integrin and MMP Genes

Key Sun Park1,7, Kee Kwang Kim1,2,7, Zheng-Hao Piao1,3, Mi Kyung Kim1, Hyun Jean Lee1, Yong Chan Kim1,4, Ki Sung Lee5, Jeung-Hoon Lee6, and Kyoon Eon Kim1,*

1Department of Biochemistry, Chungnam National University, Daejeon 305-764, Korea, 2Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA, 3Department of Basic Medical Sciences, Hangzhou Normal University School of Medicine, Xiasha Higher Education Zone, Hangzhou, China, 4Department of Medicine (MED), USUHS Building A, Bethesda, MD 20814, USA, 5Department of Biology and Medicinal Science, College of Sciences and Technology, Pai Chai University, Daejeon 302-735, Korea, 6Department of Dermatology, College of Medicine, Chungnam National University, Daejeon 301-747, Korea, 7These authors contributed equally to this work.

Correspondence to:*Correspondence: kyoonkim@cnu.ac.kr

Received: September 20, 2012; Accepted: October 10, 2012

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.

Keywords: B16F10 cells, cancer, metastasis, OLFM4, tumor growth

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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