Microbiology, Immunology and Molecular Genetics, Molecular Biology Interdepartmental Ph.D. Program, Departments of Molecular and Medical Pharmacology, Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Howard Hughes Medical Institute, and Department of Urology, University of California, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20111-6. doi: 10.1073/pnas.1320565110. Epub 2013 Nov 26.
The relationship between the cells that initiate cancer and the cancer stem-like cells that propagate tumors has been poorly defined. In a human prostate tissue transformation model, basal cells expressing the oncogenes Myc and myristoylated AKT can initiate heterogeneous tumors. Tumors contain features of acinar-type adenocarcinoma with elevated eIF4E-driven protein translation and squamous cell carcinoma marked by activated beta-catenin. Lentiviral integration site analysis revealed that alternative histological phenotypes can be clonally derived from a common cell of origin. In advanced disease, adenocarcinoma can be propagated by self-renewing tumor cells with an androgen receptor-low immature luminal phenotype in the absence of basal-like cells. These data indicate that advanced prostate adenocarcinoma initiated in basal cells can be maintained by luminal-like tumor-propagating cells. Determining the cells that maintain human prostate adenocarcinoma and the signaling pathways characterizing these tumor-propagating cells is critical for developing effective therapeutic strategies against this population.
启动癌症的细胞与传播肿瘤的癌症干细胞样细胞之间的关系尚未明确。在人类前列腺组织转化模型中，表达癌基因 Myc 和豆蔻酰化 AKT 的基底细胞可以启动异质性肿瘤。肿瘤具有腺泡型腺癌的特征，表现为 eIF4E 驱动的蛋白质翻译增加，以及鳞状细胞癌表现为β-catenin 激活。慢病毒整合位点分析显示，不同的组织学表型可以从起源相同的细胞克隆衍生而来。在晚期疾病中，雄激素受体低、不成熟腔状表型的自我更新肿瘤细胞可以传播腺癌，而基底样细胞缺失。这些数据表明，起源于基底细胞的晚期前列腺腺癌可以由类似腔状的肿瘤传播细胞维持。确定维持人前列腺腺癌的细胞以及表征这些肿瘤传播细胞的信号通路对于开发针对该群体的有效治疗策略至关重要。
