Introduction

Metastatic disease is a complex and multistep process that continues to be one of the most significant problems in cancer medicine. Metastatic cancer cells are unique given their ability to leave the site of the primary tumor, enter the circulation, resist phagocytosis, and grow at distant sites. At distant sites, metastatic tumor cells not only survive, but thrive in the new novel microenvironment co-opting existing blood vessels or inducing neovascularization. These factors lead to the growth of clinically significant metastases.

At the molecular level, cancer metastasis is a complex process involving the deregulation of interacting proteins and genes leading to invasion, angiogenesis, circulation of tumor cells in blood vessels, colonization at secondary organ sites, and, finally, evasion of host defense systems. These particular steps have been modeled into a “metastatic cascade” (Table 1). Recent findings suggest that to successfully metastasize, tumor cells require stem cell-like properties. Also, tumor stroma and paracrine interactions between tumor cells and non-neoplastic cells in metastatic sites probably play roles. Furthermore, it is likely that cigarette smoke exposure affects the metastatic potential of tumor cells via signal transduction effects. Germ line polymorphisms may also play a role in cancer metastases.