Bovine Holo-lactoferrin inhibits tumor growth and metastasis induced by BPA in murine triple negative breast cancer models

Breast cancer is the leading cause of cancer-related deaths in worldwide women. Triple negative breast cancer (TNBC) subtype does not express progesterone, estrogen and Her2 receptors. Bisphenol A (BPA) is an endocrine-disrupting chemical used in plastics and epoxy resins production that is associated with an increased rate of cancer including breast cancer. Lactoferrin (Lf) is a glycoprotein expressed in a variety of species that is found free of Fe ³⁺ (Apo-Lf) and associated with Fe ³⁺ (Holo-Lf). Bovine Lf (BLf) exhibits anti-tumor properties through inhibition of proliferation, migration, invasion, matrix metalloproteinases secretion, and epithelial–mesenchymal transition. In this study we demonstrate that Holo-BLf inhibits migration, invasion and assembly of focal adhesions induced by BPA in 4T1 cells, and migration in MDA-MB-231 cells. In addition, Holo-BLf inhibits the growth of mammary tumors and metastasis induced by BPA in two murine models of breast cancer using TNBC 4T1/MDA-MB-231 cells and Balb/cJ/NSG mice. In conclusion, we demonstrate, for first time, that Holo-BLf inhibits cellular processes involved with the metastasis process and the growth of mammary tumors and metastasis in two murine models of breast cancer.