Metastatic dormancy and progression in thyroid cancer: targeting cells in the metastatic frontier

Abstract

Background: Metastatic dormancy, or the ability of cancer cells to survive but not progress in metastatic environments, is now recognized to be a common occurrence in cancer.

Summary: From a clinical perspective, this phenomenon is common in metastatic well-differentiated thyroid cancer, whereby patients often present with distant metastases that remain stable for years after removal of the primary tumor and subsequent treatment. Experimental data suggest that metastases can develop throughout the life of a cancer and that progression in the distant environment depends on the biology of the cancer cells that metastasize as well as that of the various microenvironments they encounter. A firm understanding of how thyroid cancer cell progression is regulated in different metastatic environments is necessary to devise effective therapies targeting progressive metastatic thyroid cancer.

Conclusion: In this review, current models of metastatic progression and factors that regulate late-stage metastatic progression that are particularly relevant for thyroid cancer are discussed.

FIG. 1.

A model of metastatic progression in cancer. Primary tumor growth and invasion occur through the gain of genetic or epigenetic changes in the primary tumor often in cells that have a change in character through the process of epithelial to mesenchymal transition (blue cells). Individual cells, or groups of cells, that have gone through this transition, as well as those that have not (perhaps earlier in the life of the cancer), gain access to blood vessels through incompletely defined mechanisms. Some of the cells are targeted to specific organs (gold diamonds) and enter their new microenvironment. Cells that have dedifferentiated are likely able to modify the premetastatic niche to allow for proliferation and invasion with short latency in the metastatic site. Cells shed into the circulation that are more differentiated (red cells) likely enter a period of prolonged dormancy controlled by a number of factors that may be released over time through changes in the tumor cells or the metastatic microenvironment. In both cases, metastatic progression at the metastatic site likely requires interactions with immune cells, endothelial cells, and the stroma.