The Scripps Research Institute, La Jolla, California, United States of America.
PLoS One. 2012;7(2):e31226. doi: 10.1371/journal.pone.0031226. Epub 2012 Feb 16.
Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44(+)/CD133(+) prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy.
肿瘤祖细胞代表了一群耐药细胞，它们能够在常规化疗中存活下来，导致肿瘤复发。然而，肿瘤祖细胞在前列腺癌转移中的作用知之甚少。本文报道的研究表明，CXCR4/CXCL12 轴作为肿瘤扩散的关键调节剂，在维持前列腺癌干细胞样细胞中发挥作用。CD44(+)/CD133(+)前列腺祖细胞群体中激活了 CXCL4/CXCR12 通路，并影响分化潜能、细胞黏附、克隆生长和致瘤性。此外，在小鼠的前列腺肿瘤异种移植研究中表明，与单药治疗相比，靶向前列腺癌干细胞样细胞的 CXCR4 受体拮抗剂 AMD3100 与常规化疗药物 Taxotere 的联合治疗更有效地根除肿瘤。
