| Summary: | 碩士 === 國防醫學院 === 生物化學研究所 === 100 === Malignant tumors are formed due to uncontrolled cancer cell growth. Tumor cells may metastasize and invade other organs of the body. The crosstalk between cancer cells is involved in the acquired capability for invasive growth and metastasis. Evidences indicate that cancer cells secrete specific molecules to activate intrinsic downstream signaling in an autocrine or paracrine manner and thereby modulate tumor progression. To identify specific molecules secreted by cancer cells involved in tumor progression, we used EGTA（ethylene glycol tetraacetic acid）to elute the molecules associated with the tumor membrane. The EGTA eluates from breast cancer cells T47D and MCF-7, but not A549 and HEK293T, can promote cell growth. However, this stimulated cell growth can be demolished by 95℃ treatment. Three proteins, AGR2, S100A11 and 14-3-3ζ were identified by LC-MS/MS combied ith biochemical assay. Antibodies of neutralizing S100A11 and 14-3-3ζ but not AGR2 decreased the cell viability. Furthermore, 14-3-3ζbut not AGR2 and S100A11 neutralizing antibodies can block PMA-induced cell migration. Moreover, experiments with conditioned media from AGR2, S100A11 and 14-3-3ζ gene knockdown cell decreased cell viability, while conditioned media from AGR2 and 14-3-3ζ, but not S100A11silenced-cell suppressed PMA-induced cell migration. These results suggested that secreted from breast cancer cell AGR2, S100A11 and 14-3-3ζ is able to modulate the tumor progression in an autocrine and paracrine manner. AGR2 and 14-3-3ζ proteins promote cell growth and PMA-induced cell migration, while secreted S100A11 proetin involves in cell growth only. Our results indicated that S100A11, AGR2 and 14-3-3ζ might be valuable potential diagnostic markers and possible targets for breast cancer treatment. Further studies are essential to determine the mechanism of the breast cancer progression, modulated by these three proteins.
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