Faculty Bibliography

BACKGROUND: SK Hep-1 cells (SK cells) derived from a patient with liver adenocarcinoma have been considered a human hepatoma cell line with mesenchymal origin characteristics, however, SK cells do not express liver genes and exhibit liver function, thus, we hypothesized whether mesenchymal cells might contribute to human liver primary cancers. Here, we characterized SK cells and its tumourigenicity. METHODS AND PRINCIPAL FINDINGS: We found that classical mesenchymal stem cell (MSC) markers were presented on SK cells, but endothelial marker CD31, hematopoietic markers CD34 and CD45 were negative. SK cells are capable of differentiate into adipocytes and osteoblasts as adipose-derived MSC (Ad-MSC) and bone marrow-derived MSC (BM-MSC) do. Importantly, a single SK cell exhibited a substantial tumourigenicity and metastatic capacity in immunodefficient mice. Metastasis not only occurred in circulating organs such as lung, liver, and kidneys, but also in muscle, outer abdomen, and skin. SK cells presented greater in vitro invasive capacity than those of Ad-MSC and BM-MSC. The xenograft cells from subcutaneous and metastatic tumors exhibited a similar tumourigenicity and metastatic capacity, and showed the same relatively homogenous population with MSC characteristics when compared to parental SK cells. SK cells could unlimitedly expand in vitro without losing MSC characteristics, its tumuorigenicity and metastatic capacity, indicating that SK cells are oncogenic MSC with enhanced self-renewal capacity. We believe that this is the first report that human MSC appear to be transformed into cancer stem cells (CSC), and that their derivatives also function as CSCs. CONCLUSION: Our findings demonstrate that SK cells represent a transformation mechanism of normal MSC into an enhanced self-renewal CSC with metastasis capacity, SK cells and their xenografts represent a same relative homogeneity of CSC with substantial metastatic capacity. Thus, it represents a novel mechanism of tumor initiation, development and metastasis by CSCs of non-epithelial and endothelia origin.

Niels Bohr and Max Delbruck believed that complementaritysuch as wave-particle dualitywas not limited to the quantum realm, but had correlates in the study of living things. Biological complementarity would indicate that no single technique or perspective allows comprehensive viewing of all of a biological entity's complete qualities and behaviors; instead, complementary perspectives, necessarily and irrevocably excluding all others at the moment an experimental approach is selected, would be necessary to understand the whole. Systems biology and complexity theory reveal that, as in the quantum realm, experimental observations themselves limit our capacity to understand a biological system completely because of scale-dependent horizons of knowledge, a form of biological complementarity as predicted by Bohr and Delbruck. Specifically, observational selection is inherently, irreducibly coupled to observed biological systems as in the quantum realm. These nested systems, beginning with biomolecules in aqueous solution all the way up to the global ecosystem itself, are understood as a seamless whole operating simultaneously and complementarily at various levels. This selection of an observational stance is inseparable from descriptions of biology indicatesin accordance with views of thinkers such as von Neumann, Wigner, and Stappthat even at levels of scale governed by classical physics, at biological scales, observational choice remains inextricably woven into the establishment, in the observational moment, of the present conditions of existence. These conceptual shifts will not only have theoretical impact, but may point the way to new, successful therapeutic interventions, medically (at the scale of organisms) or environmentally/economically (at a global scale). (c) 2013 Wiley Periodicals, Inc. Complexity 18: 11-20, 2013