PO.MCB03.03 · 分子与细胞生物学

sFRP1在黑色素瘤中的情境依赖性作用

Context-dependent roles of sFRP1 in melanoma

海报缩略图:sFRP1在黑色素瘤中的情境依赖性作用
编号 584 展板 22 时间 4/19 02:00–05:00 区域 Section 24 主讲 Cierra Perron, BS;MS
分会场 Tumor Cell Plasticity, Microenvironment, and Stress-Response Pathways
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作者与单位 Authors & Affiliations

Cierra Perron1, Douglas Quilty1, Farzaneh Afzali1, Bianca Dauber1, Tyler Cooper2, Krista M. Vincent3, Ivan Topisirovic4, Lynne-Marie Postovit1

1Biomedical and Molecular Science, Queen's Univ. Cancer Research Inst., Kingston, ON, Canada,2Department of Obstetrics and Gynecology, Centre de recherche du Centre hospitalier de l’Université de Montréal, Montreal, QC, Canada,3Anatomy and Cell Biology, Western University, London, ON, Canada,4Department of Oncology, McGill University, Montreal, QC, Canada

摘要 Abstract

中文摘要
在黑色素瘤患者数据集中,分泌型卷曲相关蛋白1(sFRP1)水平升高与总生存期及远处无转移生存期缩短相关,提示其在疾病进展中具有临床显著意义。为探究这一关联的潜在机制,我们比较了基础sFRP1水平不同的黑色素瘤细胞系,并在sFRP1过表达或敲低后评估了增殖、迁移和侵袭。增殖采用标准实验测定,而迁移和侵袭采用划痕实验和Boyden小室实验进行定量。 在各细胞系中,sFRP1产生了不同的表型结果,表明其活性高度依赖于情境。初步机制分析提示sFRP1并非通过单一经典通路发挥作用;相反,它似乎影响肿瘤微环境的组分,包括与免疫调节通路相关的标志物。这些情境依赖性变化凸显了sFRP1在塑造黑色素瘤细胞与其周围微环境相互作用中的更广泛作用。 总体而言,这些发现支持这样一种模型:sFRP1通过多因素、微环境依赖性机制调节黑色素瘤进展,而非发挥一致的致癌或抑癌作用。sFRP1对黑色素瘤的影响似乎由个体肿瘤的内在特征所塑造。正在进行的研究旨在确定决定sFRP1驱动表型的机制、细胞外通路和肿瘤情境及其潜在临床相关性。
查看英文原文 English abstract
Elevated levels of secreted Frizzled-Related Protein 1 (sFRP1) in melanoma patient datasets correlate with reduced overall and distant metastasis-free survival, suggesting a clinically significant role in disease progression. To explore the mechanisms underlying this association, we compared melanoma cell lines with differing basal sFRP1 levels and assessed proliferation, migration, and invasion following sFRP1 overexpression or knockdown. Proliferation was measured with standard assays, while migration and invasion were quantified using scratch and Boyden chamber assays. Across cell lines, sFRP1 produced divergent phenotypic outcomes, indicating that its activity is highly context-specific. Preliminary mechanistic analyses suggest that sFRP1 does not act through a single canonical pathway; instead, it appears to influence components of the tumor microenvironment, including markers linked to immune-regulatory pathways. These context-dependent changes highlight a broader role for sFRP1 in shaping interactions between melanoma cells and their surrounding microenvironment. Overall, these findings support a model in which sFRP1 modulates melanoma progression through multifactorial, microenvironment-dependent mechanisms rather than exerting uniformly oncogenic or suppressive effects. The impact of sFRP1 on melanoma appears shaped by intrinsic features of individual tumors. Ongoing studies aim to define the mechanisms, extracellular pathways, and tumor contexts that determine sFRP1-driven phenotypes and their potential clinical relevance.
利益披露 Disclosure
C. Perron, None.. D. Quilty, None.. F. Afzali, None.. B. Dauber, None.. T. Cooper, None.. K. M. Vincent, None.. I. Topisirovic, None.. L. Postovit, None.

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