Exosomes promote pre-metastatic niche formation in colorectal cancer

Abstract

It is well known that colorectal cancer (CRC) has a high morbidity rate, a poor prognosis when metastasized, and a greatly shortened 5-year survival rate. Therefore, understanding the mechanism of tumor metastasis is still important. Based on the "seed and soil" theory, the concept of " premetastatic niche (PMN)" was introduced by Kaplan et al. The complex interaction between primary tumors and the metastatic organ provides a beneficial microenvironment for tumor cells to colonize at a distance. With further exploration of the PMN, exosomes have gradually attracted interest from researchers. Exosomes are extracellular vesicles secreted from cells that include various biological information and are involved in communication between cells. As a key molecule in the PMN, exosomes are closely related to tumor metastasis. In this article, we obtained information by conducting a comprehensive search across academic databases including PubMed and Web of Science using relevant keywords. Only recent, peer-reviewed articles published in the English language were considered for inclusion. This study aims to explore in depth how exosomes promote the formation of pre-metastatic microenvironment (PMN) in colorectal cancer and its related mechanisms.

Keywords: Colorectal cancer (CRC); Exosomes; Liver metastases; Premetastatic niche (PMN).

Fig. 1

Schematic of the role of exosomes in EMT formation. Exosomes affect EMT formation and enhance tumor aggressiveness. EMT, epithelial-mesenchymal transition; CRC, colorectal cancer; CAFs, cancer-associated fibroblasts.

Fig. 2

Schematic showing the roles of exosomes in colorectal cancer premetastatic niches. Exosomes contribute to PMN formation through multiple mechanisms, including immunosuppression by recruiting MDSCs, facilitating TAM polarization, facilitating TAN polarization, inhibiting CD8⁺ T cell activation, and inhibiting the inflammatory microenvironment, by activating CAFs and Kupffer cells to release inflammatory mediators as well as by activating angiogenesis, lymph angiogenesis, organ-specific metastasis, and metabolic reprogramming. The arrows represent activation, whereas bar-headed lines represent inhibition. CRC, colorectal cancer; CAFs, cancer-associated fibroblasts; MDSCs, myeloid-derived suppressor cells; TAM, tumor-associated macrophage; TAN, tumor-associated neutrophil; HSC, hepatic stellate cell.