School of Nursing, Faculty of Health Sciences, Universidad Bernardo O'Higgins, Santiago 8370854, Chile.
Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Biomedical Sciences Institute (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8370854, Chile.
Int J Mol Sci. 2024 Oct 31;25(21):11709. doi: 10.3390/ijms252111709.
Kinin receptors B1 and B2 are involved in migration and invasion in gastric, glioma, and cervical cancer cells, among others. However, the role of kinin receptors in breast cancer cells has been poorly studied. We aimed to reveal the impact of B1 and B2 receptors on migration and invasion in breast cancer cells and demonstrate their capacity to modulate in vivo tumor growth. MDA-MB-231, MCF-7, and T47D cells treated with Lys-des[Arg]bradykinin (LDBK) or bradykinin (BK) were used to evaluate migration and invasion. Des-[Arg]-Leu-BK and HOE-140 were used as antagonists for the B1 and B2 receptors. MDA-MB-231 cells incubated or not with antagonists were subcutaneously inoculated in BALBc NOD/SCID mice to evaluate tumor growth. LDBK and BK treatment significantly increased migration and invasion in breast cancer cells, effects that were negated when antagonists were used. The use of antagonists in vivo inhibited tumor growth. Moreover, the migration and invasion induced by kinins in breast cancer cells were inhibited when focal adhesion kinase (FAK) and Src inhibitors were used. The novelty revealed in our work is that B1 and B2 receptors activated by LDBK and BK induce migration and invasion in breast cancer cells via a mechanism that involves the FAK-Src signaling pathway, and the antagonism of both receptors in vivo impairs breast tumor growth.
缓激肽受体 B1 和 B2 参与胃癌、神经胶质瘤和宫颈癌等多种癌症细胞的迁移和侵袭。然而，缓激肽受体在乳腺癌细胞中的作用尚未得到充分研究。我们旨在揭示 B1 和 B2 受体对乳腺癌细胞迁移和侵袭的影响，并证明它们调节体内肿瘤生长的能力。使用 Lys-des[Arg]bradykinin (LDBK) 或缓激肽 (BK) 处理 MDA-MB-231、MCF-7 和 T47D 细胞，以评估迁移和侵袭。Des-[Arg]-Leu-BK 和 HOE-140 被用作 B1 和 B2 受体的拮抗剂。将 MDA-MB-231 细胞与拮抗剂孵育或不孵育，然后皮下接种于 BALBc NOD/SCID 小鼠中，以评估肿瘤生长。LDBK 和 BK 处理显著增加了乳腺癌细胞的迁移和侵袭，当使用拮抗剂时，这种作用被否定。体内使用拮抗剂抑制了肿瘤生长。此外，当使用粘着斑激酶 (FAK) 和Src 抑制剂时，缓激肽在乳腺癌细胞中诱导的迁移和侵袭被抑制。我们的工作揭示的新颖之处在于，LDBK 和 BK 激活的 B1 和 B2 受体通过涉及 FAK-Src 信号通路的机制诱导乳腺癌细胞的迁移和侵袭，并且体内拮抗这两种受体可损害乳腺肿瘤的生长。
