Mechanisms of Metastasis

Almost all deaths in cancer are attributable to metastatic colonization of distant tissue and not to organ failure at from the primary tumor. The process of metastasis, or the spread of cancer cells from the primary tumor to distant sites in the body, involves a complex series of interconnected biological processes orchestrated by cancer cells. Initially, cancer cells acquire invasive properties through changes in gene expression and signaling pathways, allowing them to detach from the primary tumor and invade surrounding tissues. This process is facilitated by proteolytic enzymes that enable cancer cells to penetrate blood vessels or lymphatic vessels, with a strong selective pressure on these cells to evade immune surveillance and survive shear forces by adopting a dormant or quiescent state. Upon reaching a secondary sites, cancer cells can extravasate into the tissue parenchyma, aided by adhesion molecules and chemokines to adapt to the new microenvironment, proliferate, and establish metastatic colonies. The intricate mechanisms of metastasis involve a combination of genetic, epigenetic, and microenvironmental factors, making it a challenging aspect of cancer biology to understand and target therapeutically.

The ability of these cells to evade immunity and their ability to be targeted is a focus for work in our laboratory. Our studies have identified that many tumors are aided by inflammatory immune signaling axis to spread and can evade immunity in different manners, depending on the context of their metastatic site. While these sites vary, most cancers preferentially metastasize to specific organ sites, thus presenting an opportunity to specifically target immune suppressive mechanisms at an early stage of metastatic dissemination.