Autophagy stimulation influenced the angiogenesis and metastasis behavior of human triple-negative breast cancer cells
Articles > Article · 2025
Authors: Zahra Abbasi-Malati, Çığır Biray Avci, Parisa Khanicheragh, Zeinab Aliyari Serej, Maryam Sabour Takanlou, Leila Sabour Takanlou, Seyed Ghader Azizi, Reza Rahbarghazi, Zohreh Sanaat, Nafiseh Didar Khosrowshahi, Hassan Amini, Rasoul Hosseinpour
BioImpacts, International, WoS, 2025, vol 15, pp 32624-32624
DOI: 10.34172/bi.32624
Summary
Introduction: Breast cancer (BC) is a devastating condition with high morbidity and mortality rates in females. Autophagy is an early-stage cell response against stressful conditions. Emerging data have revealed the autophagy-angiogenesis interaction in terms of tumor development and metastasis. Methods: Here, the angiogenesis behavior of human MDA-MB-231 cells was monitored after modulation of autophagy response in the presence of free 3-methyladenine (3-MA), metformin (Met), or drug-loaded exosomes (3-MA@Exos and Met@Exos). Orthotopic transplantation was done using human BC cell-laden alginate/gelatin (Alg/Gel) microspheres in mice after treatment with Met and/or 3-MA. Results: Met, and/or Met@Exos increased the cell migration rate and promoted human endothelial cell migration compared to the control cells (P < 0.05). However, these features were blunted in 3-MA and 3-MA@Exos groups (P < 0.05). Flow cytometry analysis revealed that the drug loading into Exos did not influence internalization capacity or cell survival (P > 0.05). ELISA revealed that vascular endothelial growth factor (VEGF) levels were reduced in Met and 3-MA-treated cells, with more pronounced reductions in the free 3-MA groups. Real-time PCR analysis showed diminished expression of several angiogenesis-related genes, except for platelet endothelial cell adhesion molecule-1 (PECAM-1) in the Met@Exos, 3-MA, and 3-MA@Exos groups. Met treatment increased the metastasis and tumor formation in mice mammary glands after orthotopic transplantation of BC tumoroids. Conclusion: These data indicate that autophagy modulation can alter the angiogenesis and metastatic behavior of human BC cells in vitro and in vivo. Exos are valid bio-shuttles for the delivery of autophagy modulators in CSC-targeted therapies.