Houston Michele A, Augenlicht Leonard H, Heerdt Barbara G
Department of Oncology, Albert Einstein Cancer Center, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA.
Int J Cell Biol. 2011;2011:978583. doi: 10.1155/2011/978583. Epub 2011 Jul 2.
Heterogeneity among cells that constitute a solid tumor is important in determining disease progression. Our previous work established that, within a population of metastatic colonic tumor cells, there are minor subpopulations of cells with stable differences in their intrinsic mitochondrial membrane potential (ΔΨm), and that these differences in ΔΨm are linked to tumorigenic phenotype. Here we expanded this work to investigate primary mammary, as well as colonic, tumor cell lines. We show that within a primary mammary tumor cell population, and in both primary and metastatic colonic tumor cell populations, there are subpopulations of cells with significant stable variations in intrinsic ΔΨm. In each of these 3 tumor cell populations, cells with relatively higher intrinsic ΔΨm exhibit phenotypic properties consistent with promotion of tumor cell survival and expansion. However, additional properties associated with invasive potential appear in cells with higher intrinsic ΔΨm only from the metastatic colonic tumor cell line. Thus, it is likely that differences in the intrinsic ΔΨm among cells that constitute primary mammary tumor populations, as well as primary and metastatic colonic tumor populations, are markers of an acquired tumor phenotype which, within the context of the tumor, influence the probability that particular cells will contribute to disease progression.
构成实体瘤的细胞之间的异质性在决定疾病进展方面很重要。我们之前的研究表明，在转移性结肠肿瘤细胞群体中，存在少数亚群细胞，其内在线粒体膜电位（ΔΨm）存在稳定差异，并且这些ΔΨm的差异与致瘤表型相关。在此，我们扩展了这项研究，以调查原发性乳腺肿瘤细胞系以及结肠肿瘤细胞系。我们发现，在原发性乳腺肿瘤细胞群体中，以及在原发性和转移性结肠肿瘤细胞群体中，都存在内在ΔΨm有显著稳定变化的亚群细胞。在这3种肿瘤细胞群体中的每一种中，内在ΔΨm相对较高的细胞表现出与促进肿瘤细胞存活和增殖相一致的表型特征。然而，仅在转移性结肠肿瘤细胞系中，具有较高内在ΔΨm的细胞才表现出与侵袭潜能相关的其他特征。因此，构成原发性乳腺肿瘤群体以及原发性和转移性结肠肿瘤群体的细胞之间内在ΔΨm的差异很可能是一种获得性肿瘤表型的标志物，在肿瘤环境中，这种表型会影响特定细胞促成疾病进展的可能性。
