Systematic analysis of secreted proteins reveals synergism between IL6 and other proteins in soft agar growth of MCF10A cells

<p>Abstract</p> <p>Introduction</p> <p>Breast cancer, the most common malignancy in women, still holds many secrets. The causes for non-hereditary breast cancer are still unknown. To elucidate any role for circulating naturally secreted proteins, a screen of secreted proteins' influence of MCF10A cell anchorage independent growth was set up.</p> <p>Methods</p> <p>To systematically screen secreted proteins for their capacity to transform mammalian breast epithelial cells, a soft agar screen of MCF10A cells was performed using a library of ~ 470 secreted proteins. A high concentration of infecting viral particles was used to obtain multiple infections in individual cells to specifically study the combined effect of multiple secreted proteins.</p> <p>Results</p> <p>Several known breast cancer factors, such as Wnt, FGF and IL were retained, as well as factors that were previously unknown to have a role in breast cancer, such as paraoxonase 1 and fibroblast growth factor binding protein 2. Additionally, a combinatory role of Interleukin 6 with other factors in MCF10A anchorage-independent growth is demonstrated.</p> <p>Conclusion</p> <p>The transforming effect of combinations of IL6 with other secreted proteins allows studying the transformation of mammary epithelial cells <it>in vitro</it>, and may also have implications in <it>in vivo </it>studies where secreted proteins are upregulated or overexpressed.</p