Phenotypic heterogeneity and instability of human ovarian tumor-initiating cells

• DOI: 10.1073/pnas.1005529108
• Publication Date: 2011-03-31T03:50:52Z
• Authors: Jocelyn M. Stewart; Patricia A. Shaw; Craig Gedye; Marcus Q. Bernardini; Benjamin G. Neel; Laurie E. Ailles
• Keywords: Mice, Knockout; Ovarian Neoplasms; 0301 basic medicine; Transplantation, Heterologous; Mice, SCID; Models, Biological; 3. Good health; Mice; 03 medical and health sciences; Mice, Inbred NOD; Neoplastic Stem Cells; Animals; Humans; Female

The cancer stem cell (CSC) model proposes that tumors have a hierarchical organization in which only some cells indefinitely self-renew and thereby sustain tumor growth. In addition, the CSC requires tumor-initiating (TICs) be prospectively isolatable on basis of their phenotype. Previous studies suggested serous ovarian (SOC) conforms to model, but these used arguably nonfidelitous immortalized lines, cultured primary cells, or passaged xenografts as source cells. We developed robust assay for quantifying TICs from SOC. Using this assay, we find are rare when assayed either NOD/SCID NOD/SCID/IL2Rγ −/− (NSG) mice. TIC frequency (TICf) varies substantially between patients, although it is similar masses omental metastases, suggesting TICf an intrinsic property tumors. CD133 marks all several SOC cases. However, other cases, substantial activity found both + − fractions, whereas still cases exclusively TICs. Furthermore, phenotype can change xenografts: give rise contain numbers Our results highlight need quantitative rigor evaluation caution using such studies. our data suggest hypothesis, heterogeneity may complicate its clinical application.