Resumen de TRPS1 knockdown inhibits angiogenic vascular mimicry in human triple negative breast cancer cells
M. Wu, X. Sun, T. Wang, M. Zhang, P. Li
Purpose Vascular mimicry (VM) tubules are lumen structures comprised of malignant tumor cells without the participation of endothelial cells. VM simulates blood vessel function in tumors to deliver a sufcient blood supply for proliferation, invasion, and metastasis of malignant tumors, thereby reducing the clinical efects of anti-angiogenic treatments. The elimination or prevention of malignant tumor VM development therefore represents an urgent research goal as a therapeutic strategy to and cut of nutrients required for tumor growth. The GATA transcription factor TRPS1 is abnormally up-regulated in breast cancer, osteosarcoma, prostate cancer, and other tumor tissues, and is instrumental in regulating cell proliferation, diferentiation, and tissue growth and development.
Methods Here, we explored the efects of TRPS1 knockdown on VM and the proteins underlying its development in triplenegative breast cancer cell line MDA-MB-231.
Results We found that TRPS1 knockdown resulted in obvious inhibition of VM development. Fluorescence microscopy of F-actin and tubulin revealed that loss of TRPS1 function resulted in disruption of cytoskeleton and microtubule formation, respectively. In addition, TRPS1-suppressed cells exhibited reduced accumulation of VM-associated proteins EphA2, MMP-2, MMP-9, VEGF, and VE-cadherin. Moreover, it is interesting to know that the capacity for migration and invasion were limited in MDA-MB-231cells after TRPS1 knockdown and that the average number of VM tubules, their length, and number of intersections were also signifcantly decreased.
Conclusions Based on our results, and in light of previous studies, we thus proposed that TRPS1 suppression negatively afects vascular mimicry possibly through reduced TRPS1-mediated transcriptional regulation of VM-related protein VEGF-A.
