Zhang Shi-Neng, Huang Feng-Ting, Huang Yi-Jun, Zhong Wa, Yu Zhong
Department of Gastroenterology The Second Affiliated Hospital of Sun Yat-Sen University Guangzhou, People's Republic of China.
Tumori. 2010 Nov-Dec;96(6):985-92.
To identify and partially characterize the side population cells derived from three human pancreatic adenocarcinoma cell lines.
Side population cells were sorted from the human pancreatic adenocarcinoma cell lines SW1990, Capan-2, and BxPC-3 using flow cytometry and then analyzed for cell proliferation, clone formation, differentiation, chemoresistance, invasive potential, and tumorigenicity in a mouse model.
Human pancreatic carcinoma cell lines SW1990, Capan-2, and BxPC-3 contain 2.7% +/- 0.35%, 3.6% +/- 1.2%, and 2.8% +/- 0.8% side population cells, respectively. We further investigated cancer stem cell characteristics with the moderately differentiated human pancreatic adenocarcinoma cell line SW1990. Flow cytometry analysis revealed that side population cells could differentiate into side population and non-side population cells and could exhibit differentiation potential. Using a clone formation assay, side population cells were shown to have a higher proliferation than non-side population cells. Compared to non-side population cells, side population cells were also more resistant to gemcitabine, a commonly used anti-cancer agent against pancreatic carcinoma, and were more invasive. Importantly, the CD133 level in side population cells was significantly higher than that in non-side population cells. The enhanced tumorigenecity was further confirmed in a male diabetic/severe combined immunodeficiency mouse model. As few as 3 x 10(3) side population cells were sufficient to induce tumor formation in the mouse model, compared to 10(7) non-side population or unsorted cells.
Side population cells isolated from human pancreatic adenocarcinoma cell lines harbor cancer stem cell-like properties that may be related to the invasive potential and therapeutic-resistance of pancreatic adenocarcinoma.
鉴定并部分表征源自三种人胰腺腺癌细胞系的侧群细胞。
使用流式细胞术从人胰腺腺癌细胞系SW1990、Capan-2和BxPC-3中分离侧群细胞，然后在小鼠模型中分析其细胞增殖、克隆形成、分化、化疗耐药性、侵袭潜能和致瘤性。
人胰腺癌细胞系SW1990、Capan-2和BxPC-3分别含有2.7%±0.35%、3.6%±1.2%和2.8%±0.8%的侧群细胞。我们进一步用人胰腺中分化腺癌细胞系SW1990研究癌症干细胞特征。流式细胞术分析显示，侧群细胞可分化为侧群细胞和非侧群细胞，并具有分化潜能。通过克隆形成试验表明，侧群细胞比非侧群细胞具有更高的增殖能力。与非侧群细胞相比，侧群细胞对常用的胰腺癌抗癌药物吉西他滨也更具耐药性，且侵袭性更强。重要的是，侧群细胞中的CD133水平显著高于非侧群细胞。在雄性糖尿病/严重联合免疫缺陷小鼠模型中进一步证实了其增强的致瘤性。与10⁷个非侧群细胞或未分选细胞相比，低至3×10³个侧群细胞就足以在小鼠模型中诱导肿瘤形成。
从人胰腺腺癌细胞系中分离出的侧群细胞具有类似癌症干细胞的特性，这可能与胰腺腺癌的侵袭潜能和治疗耐药性有关。
