Department of Pathology, Ohio State University Medical Center, Columbus, Ohio, United States of America.
PLoS One. 2007 Mar 14;2(3):e293. doi: 10.1371/journal.pone.0000293.
Cancer stem cells (CSCs) have been identified in hematopoietic and solid tumors. However, their precursors-namely, precancerous stem cells (pCSCs) -have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into cancer, they often develop, however, into leukemic or solid cancers composed of various types of cancer cells in immunodeficient mice. The progress of the pCSCs to cancers is associated with the up-regulation of c-kit and Sca-1, as well as with lineage markers. Mechanistically, the pCSCs are regulated by the PIWI/AGO family gene called piwil2. Our results provide clear evidence that a single clone of pCSCs has the potential for both benign and malignant differentiation, depending on the environmental cues. We anticipate pCSCs to be a novel target for the early detection, prevention, and therapy of cancers.
癌症干细胞（CSCs）已在造血系统和实体肿瘤中被鉴定出来。然而，它们的前体细胞——即癌前干细胞（pCSCs）——尚未被表征。在这里，我们通过实验确定了 pCSCs，这些细胞具有良性和恶性分化的潜力，具体取决于环境线索。虽然克隆性 pCSCs 在免疫功能正常的小鼠中可以分化为各种类型的组织细胞而不发展为癌症，但它们通常在免疫缺陷小鼠中发展为白血病或由各种类型的癌细胞组成的实体癌。pCSCs 向癌症的进展与 c-kit 和 Sca-1 的上调以及谱系标记物有关。从机制上讲，pCSCs 受称为 piwil2 的 PIWI/AGO 家族基因调控。我们的结果提供了明确的证据，表明单个 pCSC 克隆具有良性和恶性分化的潜力，具体取决于环境线索。我们预计 pCSCs 将成为癌症早期检测、预防和治疗的新靶点。
