A novel role of IGFBP5 in the migration, invasion and spheroids formation induced by IGF-I and insulin in MCF-7 breast cancer cells.

IF 3 3区 医学 Q2 ONCOLOGY Breast Cancer Research and Treatment Pub Date : 2024-11-01 Epub Date: 2024-06-19 DOI:10.1007/s10549-024-07397-5
Karem Rodríguez-Rojas, Pedro Cortes-Reynosa, Pablo Torres-Alamilla, Nínive Rodríguez-Ochoa, Eduardo Perez Salazar
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Abstract

Purpose: The insulin-like growth factor (IGF) system includes IGF-I, IGF-II insulin and their membrane receptors. IGF system also includes a family of proteins namely insulin-like growth factor-binding proteins (IGFBPs) composed for six major members (IGFBP-1 to IGFBP6), which capture, transport and prolonging half-life of IGFs. However, it has been described that IGFBPs can also have other functions.

Methods: IGFBP5 expression was inhibited by shRNAs, migration was analyzed by scratch-wound assays, invasion assays were performed by the Boyden chamber method, spheroids formation assays were performed on ultra-low attachment surfaces, expression and phosphorylation of proteins were analyzed by Western blot.

Results: IGFBP5 is a repressor of IGF-IR expression, but it is not a repressor of IR in MCF-7 breast cancer cells. In addition, IGFBP5 is a suppressor of migration and MMP-9 secretion induced by IGF-I and insulin, but it does not regulate invasion in MCF-7 cells. IGFBP5 also is a repressor of MCF-7 spheroids formation. However treatment with 340 nM rescues the inhibitory effect of IGFBP in the MCF-7 spheroids formation.

Conclusion: IGFBP5 regulates IGF-IR expression, migration and MMP-9 secretion induced by IGF-I and/or insulin, and the spheroids formation in MCF-7 breast cancer cells.

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IGFBP5在IGF-I和胰岛素诱导的MCF-7乳腺癌细胞迁移、侵袭和球体形成中的新作用。
目的:胰岛素样生长因子(IGF)系统包括 IGF-I、IGF-II 胰岛素及其膜受体。胰岛素样生长因子系统还包括一个蛋白质家族,即胰岛素样生长因子结合蛋白(IGFBPs),由六个主要成员(IGFBP-1 至 IGFBP6)组成,可捕获、转运和延长胰岛素样生长因子的半衰期。然而,有研究表明 IGFBPs 还具有其他功能:方法:用 shRNAs 抑制 IGFBP5 的表达,用划痕法分析迁移,用 Boyden 室法进行侵袭试验,在超低附着面上进行球体形成试验,用 Western 印迹法分析蛋白质的表达和磷酸化:结果:IGFBP5是IGF-IR表达的抑制因子,但在MCF-7乳腺癌细胞中不是IR的抑制因子。此外,IGFBP5 还是 IGF-I 和胰岛素诱导的迁移和 MMP-9 分泌的抑制因子,但它并不调控 MCF-7 细胞的侵袭。IGFBP5 还是 MCF-7 球形细胞形成的抑制因子。然而,用 340 nM 处理可挽救 IGFBP 对 MCF-7 球形细胞形成的抑制作用:结论:IGFBP5调节IGF-IR的表达、IGF-I和/或胰岛素诱导的迁移和MMP-9的分泌,以及MCF-7乳腺癌细胞球形体的形成。
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来源期刊
CiteScore
6.80
自引率
2.60%
发文量
342
审稿时长
1 months
期刊介绍: Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.
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