據(jù)臺灣媒體報道,,臺灣“中研院”基因體研究中心針對乳癌干細胞表面上的多醣抗原物質(zhì)進行研究,,獲得重大突破,,證實乳癌干細胞的表面存有“Globo H”以及“Gb5”醣分子,,未來可針對此醣分子研發(fā)抗乳癌疫苗,。
臺“中研院”發(fā)布新聞指出,,科學界近年來的研究顯示,,癌癥細胞中也有干細胞的存在。這些癌癥干細胞具有自力更生與分化新細胞的特殊能力,,因此可能是癌癥生長的源頭,;未來以癌癥干細胞為治療的主要標的,成為最新的研究趨勢,。
目前已有以“Globo H”作為對象所開發(fā)出的乳癌治療性疫苗,,可刺激患者免疫系統(tǒng)產(chǎn)生抗體反應,利用自體的免疫力量消滅癌細胞,。近日在基因體研究中心副主任陳鈴津主持下,,研究結果證實“Globo H”以及“Gb5”都會表現(xiàn)在乳癌干細胞的表面,也將可協(xié)助研究小組設計出更新,、更有效力的下一代抗乳癌疫苗,。
另外,“中研院”院長翁啟惠領導的研究團隊更針對“Globo H”及其類似物,,進行生物芯片的研究,。這項生物芯片用來測試病患所產(chǎn)生的自體免疫反應有更快速的效果。
日前相關的兩篇論文同時獲刊于國際重量級刊物美國《國家科學院院刊》(Online EarlyEdition of PNAS, Proceedings of the National Academy of Sciences),。報道稱,,這項重要研究成果將提供乳癌治療新的思考方向。(生物谷Bioon.com)
生物谷推薦原始出處:
PNAS,,doi: 10.1073/pnas.0804979105,,Wen-Wei Chang, Alice L. Yu
Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyl transferases 1 and 2 in Globo H synthesis
Wen-Wei Chang*,†, Chien Hsin Lee*,†, Peishan Lee*, Juway Lin*,‡, Chun-Wei Hsu*, Jung-Tung Hung*, Jin-Jin Lin*, Jyh-Cherng Yu§, Li-en Shao*, John Yu*,¶, Chi-Huey Wong*,‖, and Alice L. Yu*,‖
Abstract
We examined the expression in breast cancer stem cells (BCSCs) of Globo H, a potential tumor-associated antigen for immunotherapy of epithelial cancers including breast cancer. Flow cytometry revealed Globo H expression in 25/41 breast cancer specimens (61.0%). Non-BCSCs from 25/25 and BCSCs from 8/40 (20%) expressed Globo H. We showed the expression of stage-specific embryonic antigen 3 (SSEA3), the pentasaccharide precursor of Globo H, in 31/40 (77.5%) tumors. Non-BCSCs from 29/31 and BCSCs from 25/40 (62.5%) expressed SSEA3. Like Globo H, SSEA3 expression in normal tissues was predominately at the secretory borders of epithelium, where access to the immune system is restricted. Immunization of mice with Globo H-KLH and α-GalCer induced antibodies reactive with Globo H and SSEA3, suggesting that a Globo H-based vaccine will target tumor cells expressing Globo H or SSEA3. We next sought to reduce Globo H expression by siRNA targeting fucosyltransferase (FUT) 1 and 2, which mediate alpha-1,2 linkage of fucose to SSEA3 to generate Globo H. We showed both genes to be involved in the biosynthesis of Globo H. Moreover, FUT2 expression in BCSCs was significantly lower than in non-BCSCs harvested from a primary human breast cancer in NOD/SCID mouse, whereas FUT1 was slightly lower in BCSCs. Thus, the lower expression of Globo H in BCSCs may be attributed to less FUT2/FUT1, and to reduced SSEA3 in BCSCs compared with non-BCSCs. Our findings provide insight into further development of a Globo H-based vaccine and FUT1/FUT2-targeted therapy for breast cancer.