Leukocytes as paracrine regulators of metastasis and determinants of organ-specific colonization

Abstract

It is now well recognized that tumor cell-host interactions regulate all aspects of cancer development. Amongst the various host response programs that facilitate primary cancer development, an emerging body of literature points to a critical role for leukocytes and their soluble mediators as regulating discrete events during primary tumor development and metastasis. This review focuses on the multiple aspects of leukocytes and their effector molecules as regulators of the metastatic process.

Figure. Immune signaling in tumor microenvironments facilitates all stages of tumorigenesis

Soluble mediators secreted by infiltrating and resident leukocytes and by carcinoma-associated fibroblasts (CAFs) within primary tumor sites support signaling programs within neoplastic cells that enable motile and invasive growth. Survival of circulating tumor cells (CTCs) in peripheral blood is facilitated by platelets, neutrophils and production of selectins and chemokine receptors. Organ-specific metastasis is directed by differential expression of chemokines and their receptors that together promote extravasation and retention of CTCs in distal organs. Colonization of distal organs is accomplished by mobilization of leukocytes and other stromal cells in ectopic organs, such as activation of osteoclasts in bone, and recruitment of glial cells in brain.