Tumor cell invasion and metastasis in vivo

For a number of solid tumors, although the primary tumor may be removed by surgery, patients succumb to the disease due to spread of the tumor before surgery to other tissues, termed metastasis. We have studied the process of metastasis of breast cancer using in vitro and mouse models. Metastasis involves the local invasion of tumor cells into surrounding tissue, entry into blood vessels, travel through the bloodstream to distant sites such as the lung, arrest in the vasculature of the lung, extravasation into the lung, and growth. As a lung metastasis gets larger, it in turn can repeat this cycle, resulting in the spread of metastases throughout the body and eventual death of the patient. We have found that tumor associated macrophages can enhance a number of the steps of metastasis through paracrine interactions with tumor cells. In particular we have found and EGFR/CSF1R paracrine interaction to be important, in which CSF1 produced by tumor cells can stimulate nearby macrophages to in turn secrete EGF receptor ligands that can stimulate the tumor cells. This paracrine interaction can enhance local invasion and intravasation, resulting in increased metastatic capability.