Although stem cells are critical to tissue repair, several studies indicate that they also may have important roles in malignant transformation and cancer initiation (2–4). Experimental evidence indicates that gastric cancer may originate from bone marrow–derived cells (3), and that osteosarcomas may be derived from MSC (4). Furthermore, several reports show that MSC may support tumor growth and development of metastasis in vivo (5, 6). On the other hand, MSC have also been shown to have tumor suppressor activity. For instance, it has been shown that MSC can inhibit the malignant phenotypes of human liver cancer cell lines, which include proliferation, colony-forming ability, and oncogene expression both in vitro and in vivo (7). A suppressor function of MSC has also been observed for tumor cells of hematopoietic origin (8).

Antley-Bixler syndrome (ABS) represents a group of heterogeneous disorders characterized by skeletal, cardiac, and urogenital abnormalities that have frequently been associated with mutations in fibroblast growth factor receptor 2 or cytochrome P450 reductase genes. In some ABS patients, reduced activity of the cholesterogenic cytochrome P450 CYP51A1, an ortholog of the mouse CYP51, and accumulation of lanosterol and 24,25-dihydrolanosterol has been reported, but the role of CYP51A1 in the ABS etiology has remained obscure. To test whether Cyp51 could be involved in generating an ABS-like phenotype, a mouse knock-out model was developed that exhibited several prenatal ABS-like features leading to lethality at embryonic day 15. Cyp51(-/-) mice had no functional Cyp51 mRNA and no immunodetectable CYP51 protein. The two CYP51 enzyme substrates (lanosterol and 24,25-dihydrolanosterol) were markedly accumulated. Cholesterol precursors downstream of the CYP51 enzymatic step were not detected, indicating that the targeting in this study blocked de novo cholesterol synthesis. This was reflected in the up-regulation of 10 cholesterol synthesis genes, with the exception of 7-dehydrocholesterol reductase. Lethality was ascribed to heart failure due to hypoplasia, ventricle septum, and epicardial and vasculogenesis defects, suggesting that Cyp51 deficiency was involved in heart development and coronary vessel formation. As the most likely downstream molecular mechanisms, alterations were identified in the sonic hedgehog and retinoic acid signaling pathways. Cyp51 knock-out mice provide evidence that Cyp51 is essential for embryogenesis and present a potential animal model for studying ABS syndrome in humans.

Transmembrane protein CD9 is glioblastoma biomarker, relevant for maintenance of glioblastoma stem cells

Mesenchymal stem cells differentially affect the invasion of distinct glioblastoma cell lines

Heterogeneous glioblastoma cell cross-talk promotes phenotype alterations and enhanced drug resistance