title: Olfactomedin 4 suppresses tumor growth and metastasis of mouse melanoma cells through downregulation of integrin and MMP genes.
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.
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Key Sun
authors.initials: KS
authors.lastname: Park
authors.forename: Kee Kwang
authors.initials: KK
authors.lastname: Kim
authors.forename: Zheng-Hao
authors.initials: ZH
authors.lastname: Piao
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Hyun Jean
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Kim
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Lee
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyoon Eon
authors.initials: KE
authors.lastname: Kim
mesh_terms: D000818:Animals; D002470:Cell Survival; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D039423:Integrin alpha1 / Q000235:genetics / Q000378:metabolism; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D014407:Tumor Cells, Cultured
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D039423:Integrin alpha1; D039503:Integrin alpha6; D016023:Integrins; C081451:olfactomedin; D020780:Matrix Metalloproteinase 9