Luminal A型和HER-2阳性乳腺癌的肿瘤干细胞生物学行为比较

Comparison of biological behaviors in cancer stem cells derived from Luminal A and HER-2-positive breast cancer

目的:比较人Luminal A型和HER-2阳性乳腺癌的肿瘤干细胞的生物学行为差异。方法:用Luminal A型和HER-2阳性乳腺癌组织培分离并培养原代乳腺癌细胞,获取富含肿瘤干细胞的微球体(MS);用胰酶将MS消化成单细胞(微球体细胞,MSDC),比较两类乳腺癌MSDC的体外增殖和自我更新能力、ALDH1+表型肿瘤干细胞含量,以及移植NOD/SCID小鼠后的成瘤情况。结果:Luminal A型和HER-2阳性乳腺癌组织分离的原代乳腺癌细胞均能培养出MS,但相对于Luminal A型乳腺癌,HER-2阳性乳腺癌来源的MS形成时间短,生成的MS体积大;HER-2阳性乳腺癌来源的MSDC无论在无血清或添加血清的培养基中的增殖与再生能力均明显强于Luminal A型乳腺癌来源的MSDC,且前者含ALDH1表型干细胞比例明显高于后者(均P<0.05);HER-2阳性乳腺癌的MSDC在NOD/SCID小鼠体内成瘤能力也强于Luminal A型乳腺癌来源的MSDC。结论:Luminal A型和HER-2阳性乳腺癌分离出来肿瘤干细胞生物学行为存在明显的差异,两者可能有不同肿瘤干细胞起源。

Objective： To compare the difference in biological behaviors between two types of tumor stem cells derived from human Luminal A and HER-2-positive breast cancer.Methods： Primary breast cancer cells were isolated from specimens of Luminal A and HER-2-positive breast cancer tissues and cultured, and then the mammospheres（MSs） were obtained, which were highly enriched in tumor stem cells. MSs were dissociated into single cells（mammospheres-derived cells, MSDCs） by trypsin digestion, and then the proliferative and regenerative abilities in vitro, the proportions of ALDH1＋ cell population, and the tumor formation abilities after inoculation into NOD/SCID mice were compared betweenMSDCs from the two types of breast cancer.Results： MSs formed in the primary cultured breast cancer cells either isolated from Luminal A or HER-2-positive breast cancer tissue. However, in HER-2-positive breast cancer, the MSs formation time was shorter and their volume was larger than those in Luminal A breast cancer. The proliferative and regenerative abilities in MSDCs from HER-2-positive breast cancer were significantly higher than those in MSDCs from Luminal A breast cancer either cultured in serum-free medium or medium containing serum, and the proportion of ALDH1＋ cell population in the former was significantly higher than that in the latter（all P0.05）. The tumor formation ability of MSDCs from HER-2-positive breast cancer was stronger than that of MSDCs from Luminal A breast cancer in NOD/SCID mice.Conclusion： The tumor stem cells isolated from Luminal A and HER-2-positive breast cancer have significantly different biological behaviors. So the two types of breast cancer may originate from different tumor stem cells.