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Bovine holo-lactoferrin inhibits migration and invasion in MDA-MB-231 breast cancer cells

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Abstract

Purpose

Breast cancer is the most common malignancy in developed countries and the main cause of deaths in women worldwide. Lactoferrin (Lf) is an iron-binding protein constituted for a single polypeptide chain that is folded into two symmetrical lobes that bind Fe2+ or Fe3+. Lf has the ability to reversibly bind Fe3+ and is found free of Fe3+ (Apo-Lf) or associated with Fe3+ (Holo-Lf) with a different three-dimensional conformation. However, the role of bovine Apo-Lf (Apo-BLf) and bovine Holo-Lf (Holo-BLf) in the migration and invasion induced by linoleic acid (LA) and fetal bovine serum (FBS), as well as in the expression of mesenchymal and epithelial proteins in breast cancer cells has not been studied.

Methods and results

Scratch wound assays demonstrated that Holo-BLf and Apo-BLf do not induce migration, however they differentially inhibit the migration induced by FBS and LA in breast cancer cells MDA-MB-231. Western blot, invasion, zymography and immunofluorescence confocal microscopy assays demonstrated that Holo-BLf partly inhibit the invasion, FAK phosphorylation at tyrosine (Tyr)-397 and MMP-9 secretion, whereas it increased the number and size of focal adhesions induced by FBS in MDA-MB-231 cells. Moreover, Holo-BLf induced a slight increase of E-cadherin expression in MCF-7 cells, and inhibited vimentin expression in MCF-7 and MDA-MB-231 breast cancer cells.

Conclusion

Holo-BLf inhibits cellular processes that mediate the invasion process in breast cancer cells.

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Acknowledgements

We are grateful to Nora Ruiz for her technical assistance.

Funding

This research was funded by CONACYT (255429), Mexico. Grants from CONACYT supported N R-O and K R-R.

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Authors and Affiliations

  1. Departamento de Biologia Celular, Cinvestav-IPN. Ciudad de Mexico, Av. IPN # 2508, 07360, Mexico City, Mexico

    Ninive Rodriguez-Ochoa, Pedro Cortes-Reynosa, Karem Rodriguez-Rojas, Mireya de la Garza & Eduardo Perez Salazar

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  1. Ninive Rodriguez-Ochoa
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  2. Pedro Cortes-Reynosa
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  3. Karem Rodriguez-Rojas
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  4. Mireya de la Garza
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Contributions

N R-O, K R-R: design, conduction, data analysis, methodology, validation and manuscript preparation. P C-R, MG, EPS: Conceptualization, Methodology, Writing-Review and editing, Project administration, Funding acquisition, Visualization, Supervision.

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Correspondence to Eduardo Perez Salazar.

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Rodriguez-Ochoa, N., Cortes-Reynosa, P., Rodriguez-Rojas, K. et al. Bovine holo-lactoferrin inhibits migration and invasion in MDA-MB-231 breast cancer cells. Mol Biol Rep 50, 193–201 (2023). https://doi.org/10.1007/s11033-022-07943-8

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