Luminal A 型和 HER-2 阳性乳腺癌的肿瘤干细胞 生物学行为比较
| 作者: |
1董华英,
1王伟,
1陈元文,
1包俊杰,
1陈鑫,
1吴诚义
1 海南省人民医院 乳腺外科，海南 海口 570311;2. 重庆医科大学附属第一医院 普通外科，重庆 400016 |
| 通讯: |
吴诚义
Email: NFMWK1192@hospital-cqmu.com |
| DOI: | 10.3978/.10.3978/j.issn.1005-6947.2017.11.010 |
摘要
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。
关键词：
乳腺肿瘤
肿瘤干细胞
微球体
受体，erbB-2
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。
Comparison of biological behaviors in cancer stem cells derived from Luminal A and HER-2-positive breast cancer
CorrespondingAuthor:Wu Chengyi Email: NFMWK1192@hospital-cqmu.com
Abstract
Objective: To compare the di erence 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 a er inoculation into NOD/SCID mice were compared between MSDCs 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. e proliferative and regenerative abilities in MSDCs from HER-2-positive breast cancer were signi cantly 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 signi cantly higher than that in the la er (all P<0.05). e 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: e tumor stem cells isolated from Luminal A and HER-2-positive breast cancer have signi cantly di erent biological behaviors. So the two types of breast cancer may originate from di erent tumor stem cells.
Keywords：
Breast Neoplasms
Neoplastic Stem Cells
Microspheres
Receptor
ErbB-2
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 a er inoculation into NOD/SCID mice were compared between MSDCs 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. e proliferative and regenerative abilities in MSDCs from HER-2-positive breast cancer were signi cantly 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 signi cantly higher than that in the la er (all P<0.05). e 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: e tumor stem cells isolated from Luminal A and HER-2-positive breast cancer have signi cantly di erent biological behaviors. So the two types of breast cancer may originate from di erent tumor stem cells.