Stem cells in mammary development and carcinogenesis - Implications for prevention and treatment
Stem cells in mammary development and carcinogenesis - Implications for prevention and treatment
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DOI：
10.1385/scr:1:3:207
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Wicha, Max S.
中科院分区：
文献类型：
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作者：
Dontu, Gabriela;Liu, Suling;Wicha, Max S.
近年来，在小鼠和人乳腺干细胞和祖细胞的鉴定和表征方面取得了实质性进展。此外，越来越多的证据表明，包括乳腺癌在内的多种肿瘤可能是正常干细胞和祖细胞转化的结果。与这种癌变模型一致，最近利用基于流式细胞术的细胞分选和非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠异种移植发现了具有CD24-CD44（+）表型谱系的乳腺癌干细胞群。这种癌症干细胞群中只有200个细胞能够在动物体内产生肿瘤，而大部分肿瘤群只有在大量植入时才具有致瘤性。与正常细胞一样，癌症干细胞具有自我更新的能力，能够驱动致瘤性和可能的复发转移，并具有分化的能力，从而产生肿瘤的异质性。这种干细胞癌变模型对于理解乳腺癌以及其他癌症的基本生物学具有重要意义。此外，癌症作为干细胞和祖细胞疾病的概念对癌症预防和治疗新策略的发展具有深远的意义。
Recently, substantial progress has been made in the identification and characterization of stem and progenitor cells in the mouse and human mammary gland. Furthermore, there is increasing evidence that a variety of neoplasms, including breast cancer, may result from transformation of normal stem and progenitor cells. Consistent with this model of carcinogenesis, a breast cancer stem cell population, with the phenotype CD24-CD44(+) lineage, was recently identified utilizing flow-cytometry based cell sorting and nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenografts. As few as 200 cells of this cancer stem cell population were capable of generating tumors in animals, whereas the bulk of the tumor population was tumorigenic only when implanted in high numbers. Like their normal counterparts, the cancer stem cells have the ability to self-renew, driving tumorigenicity and possibly recurrence and metastasis, and have the ability to differentiate, generating the heterogeneity of the tumors. This stem cell model of carcinogenesis has important implications for understanding the basic biology of breast cancer, as well as other cancers. Furthermore, the concept of cancer as a disease of stem and progenitor cells has profound implications for the development of new strategies for cancer prevention and therapy.