Prospective identification of tumorigenic breast cancer cells
Prospective identification of tumorigenic breast cancer cells
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DOI：
10.1073/pnas.0530291100
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发表时间：
2003-04-01
影响因子：
11.1
通讯作者：
Clarke, MF
中科院分区：
文献类型：
--
作者：
Al-Hajj, M;Wicha, MS;Clarke, MF
乳腺癌是美国妇女中最常见的恶性肿瘤，每年造成> 40，000人死亡。这些乳腺肿瘤由表型多样的乳腺癌细胞群体组成。使用人类乳腺癌细胞在免疫受损小鼠中生长的模型，我们发现只有少数乳腺癌细胞具有形成新肿瘤的能力。我们能够基于细胞表面标志物表达区分致瘤性（肿瘤起始）与非致瘤性癌细胞。我们在9名患者中的8名患者中前瞻性地鉴定并分离了CD 44（+）CD 24（-/低）谱系（-）的致瘤细胞。只有100个具有这种表型的细胞能够在小鼠中形成肿瘤，而数万个具有不同表型的细胞则无法形成肿瘤。致瘤性亚群可以连续传代：每次该群体中的细胞产生新的肿瘤，其中含有额外的CD 44（+）CD 24（-低）谱系（-）致瘤性细胞以及初始肿瘤中存在的非致瘤性细胞的表型多样性混合群体。前瞻性识别致瘤性癌细胞的能力将有助于阐明调节其生长和存活的途径。此外，由于这些细胞驱动肿瘤的发展，针对这一群体的策略可能会导致更有效的治疗。
Breast cancer is the most common malignancy in United States women, accounting for >40,000 deaths each year. These breast tumors are comprised of phenotypically diverse populations of breast cancer cells. Using a model in which human breast cancer cells were grown in immunocompromised mice, we found that only a minority of breast cancer cells had the ability to form new tumors. We were able to distinguish the tumorigenic (tumor initiating) from the non-tumorigenic cancer cells based on cell surface marker expression. We prospectively identified and isolated the tumorigenic cells as CD44(+)CD24(-/low)Lineage(-) in eight of nine patients. As few as 100 cells with this phenotype were able to form tumors in mice, whereas tens of thousands of cells with alternate phenotypes failed to form tumors. The tumorigenic subpopulation could be serially passaged: each time cells within this population generated new tumors containing additional CD44(+)CD24(-low)Lineage(-) tumorigenic cells as well as the phenotypically diverse mixed populations of nontumorigenic cells present in the initial tumor. The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival. Furthermore, because these cells drive tumor development, strategies designed to target this population may lead to more effective therapies.