Effects of Msp on the Proliferation, Migration and Invasion of Human Non-small Cell Lung Cancer Cells

LIU Xia, WEI Shi-hang, SHI Xue-ni.et al

Abstract

To determine the effects of macrophage stimulating protein (Msp) on the proliferation, migration and invasion of human non-small cell lung cancer cells PC14. Methods The eukaryotic expression vector for st1 was constructed and transfected into Msp (-) and RON (-) human non-small cell lung cancer cells PC14. The expression of st1 mRNA in PC14 cells was observed by RT-PCR. The expression levels of Msp protein in PC14, PC14-st1 -pEGFP-N1 and PC14-pEGFP-N1 groups as well as the expression of RON in PC14 and SKBR-3 cells were detected by Western blot. RAW264.7 (mouse monocyte macrophage) and SKBR-3 cells were cultured in the supernatant of cells (PC14, PC14-st1 -pEGFP-N1 and PC14-pEGFP-N1 groups) and tested with Transwell microporous membrane, through which the biologic activity of Msp was evaluated by calculating the cell number migrated. The proliferation of PC14 was measured by MTT assay. The capabilities of PC14 to migrate and invade were measured by Transwell chamber and Matrigel invasion tests, respectively. Results The expressions of mRNA and protein of Mst1 in PC14 were stable after transfection with Mst1. Msp (PC14-st1 -pEGFP-N1 group) promoted the migration of RON (+) cells (SKBR-3 and RAW264.7). Compared with PC14 and PC14-pEGFP-N1 groups, the proliferation, migration and invasion of PC14 cells in PC14-st1 -pEGFP-N1 group were inhibited significantly. Conclusion Msp can promote the migration of RON (+) cancer cells in paracrine secretion manner and inhibit the proliferation, migration and invasion of human non-small cell lung cancer cells PC14 in an unknown way.

 

Keywords: Macrophage stimulating protein, Human non-small cell lung cancer cells line, Tumor metastasis, Cell proliferation 

 


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RONSINC. MUSCATEI-LI F. MATTEI MG, et at. A novel putative receptor protein tyrosine kinase of the met family. Oncogene, 1993.8(5): 1195-1202.

IWAMA A, YAMAGUCHI N, SUDA T. ST К/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among the HGF receptor family. EMBO J. 1996, 15 ( 21 ): 5866- 5875.

PEACE BE. HUGHES MJ, DEGEN SJ, et ali. Point muta-tions and overexpression of Ron induce transformation, tumor formation, and metastasis. Oncogene, 2001, 20(43) ; 6142-6151.

WANG MH, SKEEL A, LEONARD EJ . Proteolytic cleavage and activation of pro-macrophage-stimulating protein by resident peritoneal macrophage membrane proteases. Clin Invest, 1996,97(3):720-727.

GAUDINO G, FOLLENZI A, NALDINI L, et al. RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. EMBO J, 1994 ,13( 15) :3524-3532.

SCHMIDT О, DOXAKIS E, DAVIES AM. Macrophage- stimulating protein is a neurotrophic factor for embryonic chicken hypoglossal motoneurons. Eur J Neurosci. 2002, 15 (1):101-108.

BRUNELLESCHI S, PENENGO L. LAVAGNO L, et al. Macrophage-stimulating protein ( MSP) evokes superoxide anion production by human macrophages of different origin. Br J Pharmacol,2001,134(6); 1285-1295.

LEONARD EJ. SKEEL A. A serum protein that stimulates macrophage movement, chemotaxis and spreading. Exp Cell Res,1976,102(2);434-438.

MEDICO E. MONGIOV AM, HUFF J,et al. The tyrosine kinase receptor ROn and Sea control “scattering” and morphogenesis of liver progenitor cells in -vitro. Mol Biol Cell, 1996,7(4); 495-504.

KRETSCHMANN KL, EYOB H, BUYS SS, et al. The macrophage stimulating protein/Ron pathway as a potential therapeutic target to impede multiple mechanisms involved in breast cancer progression. Curr Drug Targets, 2010, 11 ( 9 ): 1157-1168.

WELM AL, SNEDDON JB, TAYLOR C, et al. The macrophage-stimulating protein pathway promotes metastasis in a mouse model for breast cancer and predicts poor prognosis in humans. Proc Natl Acad Sci U S A, 2007, 104 (18):7570-7575.

KAKIUCHI S, DAIGO Y, TSUNODA T, et al. Genome- wide analysis of organ-preferential metastasis of human small cell lung cancer in mice. Mol Cancer Res, 2003, 1 ( 7): 485- 499.


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