In the April 3rd issue of Cell Stem Cells, Y. Liu et al. from the Univ. of Louisville Health Science Center, published their study results on the mutations in the three RB1 family members in mouse fibroblasts in forming cancer stem cells. The experimental data revealed that a loss in RB1 function can lead to a loss of contact inhibition that can result in an outgrowth of cells forming spheres in cultures. By cultivating the cells in suspension, the investigators were able to force the RB-/- cells to form spheroid bodies in which comprised a subpopulation of cancer stem cell phenotypes. The researchers noted that these cells were multipotent as well as being tumorigenic in nude mice. The authors proposed that since the RB1 pathway triggers cell cycle arrest and mediates cell-cell contact inhibition, the gene can also serve as a tumor suppressor by inhibiting cell outgrowth into three-dimensional structures that can generate cancer stem cells from terminally differentiated somatic cells in advancing cancers.

In the April 9th online edition of Stem Cells, X. He et al. from Johns Hopkins Medical Institutions reported their study on the identification and characterization of a tumorigenic subpopulation of cancer stem cells (HTCs) in urinary tumors. The investigators found in the malignant bladder epithelium (urothelial) a cellular compartment containing multipotent cancer stem cells. These cells resemble benign urothelial stem cells (basal cells) which express a 67kDa laminin receptor (67LR) and cytokeratin 17 (CK17). However, this subpopulation of HTCs did not express the carcinoembryonic antigen family member CEA-CAM6 (CD66c) and histologic analysis found these cells to reside in the tumor-stroma interface. With differential gene expression profiling of the HTCs, the researchers found that the genes were upregulated in the Jak-STAT, Notch, Focal Adhesion, mTOR, Erb, and Wnt signaling pathways. The researchers also noted that their study results showed significant overlap between the expression signatures of normal basal cells to that of the HTCs' signatures; particularly, those genes driving progression in stem cell differentiation to apoptosis. The authors surmised that their observations on understanding heterogeneity of carcinomas and HTCs can provide new therapeutic targets for cancer therapy.