Department of Veterinary Pathology, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
Res Vet Sci. 2011 Oct;91(2):254-60. doi: 10.1016/j.rvsc.2010.11.016. Epub 2010 Dec 28.
There is increasing evidence for the presence of cancer stem cells in several solid tumors, and these cancer stem cells have a potential role in tumor initiation, aggression, and recurrence. The stem cell-like properties of spheres derived from canine mammary tumors remain largely elusive. We attempted to induce sphere formation using four cell lines of canine mammary adenocarcinoma, and characterized the spheres derived from a CHMp line in vitro and in vivo. The CHMp-derived spheres showed predominantly CD44+CD24- population, higher expression of stem cell-related genes, such as CD133, Notch3 and MDR, and higher resistance to doxorubicin compared with the CHMp-derived adherent cells. Xenograft transplantations in nude mice demonstrated that only 1 × 10(4)sphere cells were sufficient for tumor formation. Use of the sphere assay on these sphere-derived tumors showed that sphere-forming cells were present in the tumors, and were maintained in serial transplantation. We propose that spheres derived from canine mammary adenocarcinoma cell lines possess a potential characteristic of cancer stem cells. Spheres derived from canine mammary tumors could be a powerful tool with which to investigate novel therapeutic drugs and to elucidate the molecular and cellular mechanisms that underlie tumorigenesis.
越来越多的证据表明，几种实体肿瘤中存在癌症干细胞，这些癌症干细胞在肿瘤的起始、侵袭和复发中具有潜在作用。犬乳腺肿瘤来源的球体的干细胞样特性在很大程度上仍难以捉摸。我们试图使用四种犬乳腺腺癌细胞系诱导球体形成，并对源自 CHMp 系的球体进行了体外和体内特征分析。与 CHMp 来源的贴壁细胞相比，CHMp 衍生的球体表现出明显的 CD44+CD24-群体，更高的干细胞相关基因（如 CD133、Notch3 和 MDR）表达，以及对阿霉素的更高抗性。裸鼠的异种移植实验表明，仅 1×10(4)个球体细胞就足以形成肿瘤。在这些球体衍生的肿瘤上使用球体测定法表明，肿瘤中存在具有球体形成能力的细胞，并且在连续移植中得以维持。我们提出，源自犬乳腺腺癌细胞系的球体具有癌症干细胞的潜在特征。源自犬乳腺肿瘤的球体可能是一种强大的工具，可用于研究新型治疗药物，并阐明肿瘤发生的分子和细胞机制。
