据台湾媒体报道,台湾“中研院”基因体研究中心针对乳癌干细胞表面上的多醣抗原物质进行研究,获得重大突破,证实乳癌干细胞的表面存有“Globo H”以及“Gb5”醣分子,未来可针对此醣分子研发抗乳癌疫苗。
台“中研院”发布新闻指出,科学界近年来的研究显示,癌症细胞中也有干细胞的存在。这些癌症干细胞具有自力更生与分化新细胞的特殊能力,因此可能是癌症生长的源头;未来以癌症干细胞为治疗的主要标的,成为最新的研究趋势。
目前已有以“Globo H”作为对象所开发出的乳癌治疗性疫苗,可刺激患者免疫系统产生抗体反应,利用自体的免疫力量消灭癌细胞。近日在基因体研究中心副主任陈铃津主持下,研究结果证实“Globo H”以及“Gb5”都会表现在乳癌干细胞的表面,也将可协助研究小组设计出更新、更有效力的下一代抗乳癌疫苗。
另外,“中研院”院长翁启惠领导的研究团队更针对“Globo H”及其类似物,进行生物芯片的研究。这项生物芯片用来测试病患所产生的自体免疫反应有更快速的效果。
日前相关的两篇论文同时获刊于国际重量级刊物美国《国家科学院院刊》(Online EarlyEdition of PNAS, Proceedings of the National Academy of Sciences)。报道称,这项重要研究成果将提供乳癌治疗新的思考方向。(生物谷Bioon.com)
生物谷推荐原始出处:
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.