Effect of CD44 binding peptide conjugated to an engineered inert matrix on maintenance of breast cancer stem cells and tumorsphere formation.
Effect of CD44 binding peptide conjugated to an engineered inert matrix on maintenance of breast cancer stem cells and tumorsphere formation.
复制标题
DOI：
10.1371/journal.pone.0059147
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jabbari E
中科院分区：
文献类型：
--
作者：
Yang X;Sarvestani SK;Moeinzadeh S;He X;Jabbari E
由于癌细胞受到微环境中许多因素的影响，一个主要的挑战是分离特定因素对癌症干细胞（CSC）的影响，同时保持其他因素不变。我们开发了一种合成惰性 3D 聚乙二醇二丙烯酸酯 (PEGDA) 凝胶培养系统，作为研究微环境因素对 CSC 反应影响的独特工具。我们报道了通过封装乳腺癌细胞在惰性 PEGDA 凝胶中形成的 CSC 将其干性保持在一定的凝胶硬度范围内。目的是研究与凝胶缀合的 CD44 结合肽 (CD44BP) 对维持乳腺 CSC 的影响。将 4T1 或 MCF7 乳腺癌细胞封装在具有 CD44BP 缀合的 PEGDA 凝胶中。对照组包括溶解的CD44BP和具有突变体CD44BP缀合的凝胶。 9天后测定肿瘤球大小和密度以及CSC标记物的表达。对于体内，将细胞封装的凝胶接种到同基因 Balb/C 小鼠中，并在 4 周后确定肿瘤形成。将 CD44BP 缀合对乳腺 CSC 维持的影响与整合素结合 RGD 肽 (IBP) 和纤连蛋白衍生的肝素结合肽 (FHBP) 进行比较。 CD44BP 与凝胶的结合可抑制体外和体内乳腺肿瘤球的形成。封装细胞在肽缀合凝胶中形成肿瘤球的能力与 CSC 标志物的表达相关。 FHBP 可增强体外肿瘤球形成，而 IBP 可消除肿瘤球形成。与凝胶中缀合的 CD44BP 和 IBP 消除了封装的 4T1 细胞的肿瘤球形成，而与不含肽的凝胶中的细胞相比，FHBP 增强了肿瘤球形成。 PEGDA水凝胶培养系统提供了一种新的工具来研究微环境中的因素对CSC维持的个体影响，而不受其他因素的干扰。
As cancer cells are affected by many factors in their microenvironment, a major challenge is to isolate the effect of a specific factor on cancer stem cells (CSCs) while keeping other factors unchanged. We have developed a synthetic inert 3D polyethylene glycol diacrylate (PEGDA) gel culture system as a unique tool to study the effect of microenvironmental factors on CSCs response. We have reported that CSCs formed in the inert PEGDA gel by encapsulation of breast cancer cells maintain their stemness within a certain range of gel stiffness. The objective was to investigate the effect of CD44 binding peptide (CD44BP) conjugated to the gel on the maintenance of breast CSCs. 4T1 or MCF7 breast cancer cells were encapsulated in PEGDA gel with CD44BP conjugation. Control groups included dissolved CD44BP and the gel with mutant CD44BP conjugation. Tumorsphere size and density, and expression of CSC markers were determined after 9 days. For in vivo, cell encapsulated gels were inoculated in syngeneic Balb/C mice and tumor formation was determined after 4 weeks. Effect of CD44BP conjugation on breast CSC maintenance was compared with integrin binding RGD peptide (IBP) and fibronectin-derived heparin binding peptide (FHBP). Conjugation of CD44BP to the gel inhibited breast tumorsphere formation in vitro and in vivo. The ability of the encapsulated cells to form tumorspheres in the peptide-conjugated gels correlated with the expression of CSC markers. Tumorsphere formation in vitro was enhanced by FHBP while it was abolished by IBP. CD44BP and IBP conjugated to the gel abolished tumorsphere formation by encapsulated 4T1 cells while FHBP enhanced tumorsphere formation compared to cells in the gel without peptide. The PEGDA hydrogel culture system provides a novel tool to investigate the individual effect of factors in the microenvironment on CSC maintenance without interference of other factors.
登录
查看更多内容
影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
影响因子：
51.1
作者：
Badve, Sunil;Nakshatri, Harikrishna
通讯作者：
Nakshatri, Harikrishna
影响因子：
3.4
作者：
Giatromanolaki, Alexandra;Sivridis, Efthimios;Koukourakis, Michael I.
通讯作者：
Koukourakis, Michael I.
影响因子：
3.9
作者：
He, Xuezhong;Yang, Xiaoming;Jabbari, Esmaiel
通讯作者：
Jabbari, Esmaiel
DOI：
10.1083/jcb.200204153
发表时间：
2002-11-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Galbraith CG;Yamada KM;Sheetz MP
通讯作者：
Sheetz MP