Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking (PNAS, 2009, 106(46):19491-19496)

報告日期: 2010/04/23
報告時間: 16:00/16:50
報告學生: 陳怡婷(英文報告)
講評老師: 王憶卿
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990423-2.pdf

Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell trafficking

PNAS, 2009, 106(46): 19491-19496

 

Speaker: Yi-Ting Chen (陳怡婷)

Commomtator: Dr. Yi-Ching Wang (王憶卿老師)     

Date: 2010/ 04/ 23 16:00-16:50

Room: 602

 

Abstract:

Mechanisms for cancer cell slow down in circulation and extravasate into target organ is still unsolved. Recently, some studies implicated that target organ in metastasis is tissue-specific but not random case. Thus, to realize the molecular regulators of cancer cell trafficking toward target organ homing might improve anti-metastasis therapies. In this study, the authors demonstrated that sialyl Lewis X (sLex) induced by α1, 3 fucosyltransferases (FT3, FT6, and FT7) was associated with bone- and liver-metastasis of prostate cancer (PCa). E-selectin on TNF-α inflamed venules was major receptor for FT3, FT6, and FT7 overexpressed PCa PC-3 cells. FT7 was underscored as a key regulator of the metastasis potential of PCa since FT7 overexpression induced PCa PC-3 cells to forcefully adhere to bone marrow endothelium (constitutive expression of E-selectin) and to inflame post-capillary by IL-1β stimulated (inducible expression of E-selectin). Furthermore, the authors pointed out that CD44, carcinoembryonic antigen (CEA), podocalyxin-like protein (PCLP), and melanoma cell adhesion molecule (MCAM), were sLex –bearing protein and E-selectin-binding ligands in the expression of α1, 3 fucosyltransferases PCa cells by Western blotting and Immunoprecipitation.

In conclusion, the novel function of α1, 3 fucosyltransferases may be relevant in regulation of cell trafficking through E-selectin-mediated adhesion. These data offer a molecular basis for how altered glyco-metabolic regulator of E-selectin ligand biosynthesis in cell trafficking that contribute to metastatic efficiency. Thus, such tissue-specific homing makers might be potent therapeutics for design of cell adhesion antagonists to prevent cancer metastasis.

 

Reference:

1.    Dimitroff CJ, et al. Rolling of human bone-metastatic prostate tumor cells on human bone marrow endothelium under shear flow is mediated by E-selectin. Cancer Res 64, 5261–5269 (2004).

2.    Martensson S, et al. Sialyl-Lewis(x) and related carbohydrate antigens in the prostate. Hum Pathol 26, 735–739 (1995).