The role of 3-mercaptopyruvate sulfurtransferase in colorectal cancer progression and tumor angiogenesis.

Research from our group and others suggests that 3-mercaptopyruvate sulfurtransferase (3-MST) regulates endothelial cell (EC) function by modulating angiogenic and bioenergetic responses and by stimulating colorectal cancer (CRC) cell proliferation. However, the role of 3-MST function in the pathophysiology of CRC-associated angiogenesis remains to be explored. In this study, we investigated the contribution of 3-MST to CRC-associated angiogenesis, blood vessel function, tumor growth, and tumor cell proliferation. We aimed to define the functional role of stable 3-MST attenuation in ECs using both in vitro angiogenesis assays and in vivo xenogeneic and syngeneic CRC mouse models. Our results show that 3-MST depletion in vitro, alone or in the presence of tumor cell-conditioned media , reduces EC proliferation, disrupts tube-like network formation, and increases monolayer permeability. In vivo, loss of 3-MST function, either in ECs co-injected with CRC cells into athymic nude mice or in the tumor microenvironment of syngeneic global 3-MST knockout mice, resulted in reduced tumor growth along with significantly reduced peritumor angiogenesis. These findings indicate that 3-MST plays a critical role in EC proliferation, tube formation, and barrier function, thereby enhancing tumor angiogenesis and ultimately affecting tumor progression, highlighting its potential as a therapeutic target for tumor-related vascular remodeling.