PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
The Inhibition of FGFR/PI3K/Akt Axis by AZD4547 Disrupts the Proangiogenic Microenvironment and Vasculogenic Mimicry Arising from the Interplay between Endothelial and Triple-Negative Breast Cancer Cells
Morales-Guadarrama, G.; Méndez-Pérez, E.A.; García-Quiroz, J.; Avila, E.; Ibarra-Sánchez, M.J.; Esparza-López, J.; García-Becerra, R.; Larrea, F.; Díaz, L. The Inhibition of the FGFR/PI3K/Akt Axis by AZD4547 Disrupts the Proangiogenic Microenvironment and Vasculogenic Mimicry Arising from the Interplay between Endothelial and Triple-Negative Breast Cancer Cells. Int. J. Mol. Sci.2023, 24, 13770.
Morales-Guadarrama, G.; Méndez-Pérez, E.A.; García-Quiroz, J.; Avila, E.; Ibarra-Sánchez, M.J.; Esparza-López, J.; García-Becerra, R.; Larrea, F.; Díaz, L. The Inhibition of the FGFR/PI3K/Akt Axis by AZD4547 Disrupts the Proangiogenic Microenvironment and Vasculogenic Mimicry Arising from the Interplay between Endothelial and Triple-Negative Breast Cancer Cells. Int. J. Mol. Sci. 2023, 24, 13770.
Morales-Guadarrama, G.; Méndez-Pérez, E.A.; García-Quiroz, J.; Avila, E.; Ibarra-Sánchez, M.J.; Esparza-López, J.; García-Becerra, R.; Larrea, F.; Díaz, L. The Inhibition of the FGFR/PI3K/Akt Axis by AZD4547 Disrupts the Proangiogenic Microenvironment and Vasculogenic Mimicry Arising from the Interplay between Endothelial and Triple-Negative Breast Cancer Cells. Int. J. Mol. Sci.2023, 24, 13770.
Morales-Guadarrama, G.; Méndez-Pérez, E.A.; García-Quiroz, J.; Avila, E.; Ibarra-Sánchez, M.J.; Esparza-López, J.; García-Becerra, R.; Larrea, F.; Díaz, L. The Inhibition of the FGFR/PI3K/Akt Axis by AZD4547 Disrupts the Proangiogenic Microenvironment and Vasculogenic Mimicry Arising from the Interplay between Endothelial and Triple-Negative Breast Cancer Cells. Int. J. Mol. Sci. 2023, 24, 13770.
Abstract
Vasculogenic mimicry (VM), a process in which aggressive cancer cells form tube-like structures, plays a crucial role in providing nutrients and escape routes. Highly plastic tumor cells, such as those with triple-negative breast cancer (TNBC) phenotype, can develop VM. However, little is known about the interplay between cellular components of the tumor microenvironment upon TNBC cells VM-capacity. In this study, we analyzed the ability of endothelial and stromal cells to induce VM when interacting with TNBC cells, and analyzed the involvement of the FGFR/PI3K/Akt pathway in this process. VM was corroborated using fluorescently‐labeled TNBC cells. Only endothelial cells triggered VM formation, suggesting a predominant role of paracrine/ juxtacrine factors from an endothelial origin in VM development. By immunocytochemistry, qPCR and secretome analyses, we determined increased expression of proangiogenic factors as well as stemness markers in VM-forming cancer cells. Similarly, endothelial cells primed by TNBC cells showed upregulation of proangiogenic molecules, including FGF, VEGFA, and several inflammatory cytokines. The endothelium-dependent TNBC-VM formation was prevented by AZD4547 or LY294002, strongly suggesting the involvement of the FGFR/PI3K/Akt axis in this process. Given that VM is associated with poor clinical prognosis, targeting FGFR/PI3K/Akt pharmacologically may hold promise for treating and preventing VM in TNBC tumors.
Keywords
co-culture; tubulogenesis; vascular mimicry; breast cancer; angiogenesis array; AZD4547; LY294002
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.