The cytokine TGF-β in colorectal cancer: mechanisms of action and secretion

Abstract

The colorectal cancer (CRC) is one of the most aggressive and lethal in humans; its incidence is increasing due to poor eating habits and a sedentary lifestyle. Genomic alterations affecting various signaling pathways contribute to this cancer development. The transforming Growth Factor-β (TGF-β) is a multifunctional cytokine that controls multiple biological effects, including the maintenance of tissue homeostasis; however, alterations in its mechanisms of action favor the development of pathologies such as fibrosis and cancer. In early stages of CRC, TGF-β exerts tumor suppressive effects, whereas it promotes tumor progression in advanced stages, which is why it is considered an important therapeutic target. This review describes and analyzes the potential mechanisms of action and secretion of TGF-β in the tumor microenvironment of CRC, focusing on the knowledge generated using human CRC cell lines: SW480 (primary tumor) and SW620 (metastatic tumor), which come from the same patient and are characterized by being very agresive. These cells synthesize and secrete high levels of TGF-β, and express the main components of its signaling pathway, such as receptors and effectors, with the exception of SMAD4 protein. Furthermore, this review is also focused on describing the composition of the extracellular vesicles secreted by SW480 and SW620 cells, and their biological effects on various types of target cells; thus, we propose that these cells can provide a model to study the mechanisms of action and secretion of TGF-β cytokine in the later stages of CRC.