Grant: Operating Grant - PA: Alberta Cancer Foundation - Research (bridge funding)

Lung cancer is the leading cause of cancer-related mortality. Most individuals diagnosed with lung cancer already have advanced disease, often accompanied by tumor spread via the blood stream to other sites. Tumors formed by these migrating cells, known as metastases, signal a greatly decreased chance survival. These 'seedlings' of the original lung cancer can differ significantly from the original tumor, and may require different treatment. Using cells from different types of human lung cancers that have been implanted in mice, we have new model systems for studying the metastases and their molecular signatures. We will find out how metastatic cells become more aggressive, and find ways to prevent and to treat metastases. In the mouse model we have found that human lung cancer cells harvested from metastatic sites (adrenal gland, bone) differ from the cell population that was originally used to generate the metastases. We propose that a key difference, i.e. over-production of growth factors, and changes in microRNA levels account for the rapid growth of the cells and the increased numbers of metastases seen when the cells are isolated from the tumors, and then re-introduced into mice. The two main areas we will study include (1) determining how it is that the metastatic cells are better at harnessing the host's cells (e.g. fibroblasts, endothelial cells, bone marrow cells) to support their growth, (2) determining which microRNAs are involved in making the metastatic cells more aggressive, and (3) whether manipulation of microRNA levels can alter their behaviour. Our future goal is to use these improved models for the testing of new ways to kill metastases.