Rodriguez-Ochoa Ninive, Cortes-Reynosa Pedro, Rodriguez-Rojas Karem, de la Garza Mireya, Salazar Eduardo Perez
Departamento de Biologia Celular, Cinvestav-IPN. Ciudad de Mexico, Av. IPN # 2508, 07360, Mexico City, Mexico.
Mol Biol Rep. 2023 Jan;50(1):193-201. doi: 10.1007/s11033-022-07943-8. Epub 2022 Nov 1.
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 Fe or Fe. Lf has the ability to reversibly bind Fe and is found free of Fe (Apo-Lf) or associated with Fe (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.
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.
Holo-BLf inhibits cellular processes that mediate the invasion process in breast cancer cells.
乳腺癌是发达国家最常见的恶性肿瘤，也是全球女性死亡的主要原因。乳铁蛋白（Lf）是一种铁结合蛋白，由一条单多肽链构成，该链折叠成两个对称的叶，可结合铁（Fe）或亚铁（Fe）。Lf具有可逆结合铁的能力，以不同的三维构象以游离铁（脱铁乳铁蛋白，Apo-Lf）或与铁结合（全乳铁蛋白，Holo-Lf）的形式存在。然而，牛脱铁乳铁蛋白（Apo-BLf）和牛全乳铁蛋白（Holo-BLf）在亚油酸（LA）和胎牛血清（FBS）诱导的迁移和侵袭以及乳腺癌细胞中间质和上皮蛋白表达中的作用尚未得到研究。
划痕试验表明，Holo-BLf和Apo-BLf不会诱导迁移，但它们能差异性地抑制FBS和LA诱导的乳腺癌细胞MDA-MB-231的迁移。蛋白质免疫印迹、侵袭、酶谱分析和免疫荧光共聚焦显微镜分析表明，Holo-BLf部分抑制侵袭、酪氨酸（Tyr）-397位点的粘着斑激酶（FAK）磷酸化和基质金属蛋白酶-9（MMP-9）的分泌，而它增加了MDA-MB-231细胞中由FBS诱导的粘着斑的数量和大小。此外，Holo-BLf诱导MCF-7细胞中E-钙粘蛋白表达略有增加，并抑制MCF-7和MDA-MB-231乳腺癌细胞中波形蛋白的表达。
Holo-BLf抑制介导乳腺癌细胞侵袭过程的细胞进程。
