Asporin increases the extracellular matrix cross-links and inhibits the cancer cell migration.

Q3 Biochemistry, Genetics and Molecular Biology
Tumor Biology Pub Date : 2025-01-01 Epub Date: 2025-03-18 DOI:10.1177/10104283241313441
Kimberly Hernandez, Caitlin H Nguyen, Girdhari Rijal
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引用次数: 0

Abstract

BackgroundMigrating strategies of the triple-negative breast cancer (TNBC) together with its role in the establishment of tumor microenvironment (TME), supporting metastasis, have been extensively studied. Extracellular matrix (ECM) is a major player for the TME, establishing the 3D spatial networks with interconnected pores necessary for the mechano-physiological function of the cells. Certain collagen aligners and cross-linkers which are necessary for the formation and the stabilization of ECM networks, however, have not been studied either in normal or in abnormal tissues. Complexities in cell-cell and cell-matrix interactions, and different in types and ratios of ECM proteins in a TME challenge to reveal the precise function of a particular protein that is exhibited by special cells and if specifically present in insignificant amount. Cancer-associated fibroblasts (CAFs) predominantly occupy the major stroma of a solid tumor where they deposit extracellular proteins in the excessive amount compared to other tumor-associated cells. For example, the TNBC tumor itself is positive for asporin (ASPN) since CAFs are major ASPN exhibitors. However, the TNBC cells express it insignificantly.ObjectiveThe increase in ECM and its networks suppresses the metastasis.MethodsHere, we studied the expression of collagen type I and ASPN in CAFS and MDA-MB-231 (MM231), and evaluated the role of ASPN in collagen alignment and crosslinking.ResultsTNBC cells have an insignificant expression of ASPN and scanty collagen fibers, some of which aggregate to form the stiff deranged fibers, forming large-size pores in ECM of cancer-cell-dominant outer core of TNBC that support cancer cell invasion and metastasis. Exogenous ASPN and fibroblast-ASPN supported for the collagen alignment and crosslinking that established the small-size pores in the ECM, inhibiting the cancer cell invasion.ConclusionsThe collagen aligner and the cross-linker, ASPN increases the ECM networks and decreases the migration, and this preliminary study provides the hope that ASPN might be used as an anti-metastatic drug after its confirmation through extensive studies in animal, and positive outcomes through preclinical trials.

菌素增加细胞外基质交联,抑制癌细胞迁移。
三阴性乳腺癌(TNBC)的迁移策略及其在肿瘤微环境(tumor microenvironment, TME)建立、支持转移中的作用已被广泛研究。细胞外基质(ECM)是TME的主要参与者,它建立了具有相互连接的孔隙的三维空间网络,这是细胞机械生理功能所必需的。然而,对于ECM网络的形成和稳定所必需的某些胶原对准剂和交联剂尚未在正常或异常组织中进行研究。细胞-细胞和细胞-基质相互作用的复杂性,以及在TME挑战中ECM蛋白的不同类型和比例,以揭示特定细胞所表现出的特定蛋白的精确功能,如果特异性地以微不足道的数量存在。癌症相关成纤维细胞(CAFs)主要占据实体瘤的主要基质,与其他肿瘤相关细胞相比,它们沉积了过量的细胞外蛋白。例如,TNBC肿瘤本身对ASPN呈阳性,因为caf是ASPN的主要表现者。而TNBC细胞表达不明显。目的ECM及其网络的增加可抑制肿瘤的转移。方法研究I型胶原和ASPN在CAFS和MDA-MB-231 (MM231)中的表达,并评价ASPN在胶原排列和交联中的作用。结果stnbc细胞中ASPN和胶原纤维的表达不明显,部分胶原纤维聚集形成僵硬的紊乱纤维,在癌细胞占主导地位的TNBC外核ECM中形成大孔,支持癌细胞的侵袭和转移。外源性ASPN和成纤维细胞ASPN支持胶原排列和交联,从而在ECM中建立小尺寸孔隙,抑制癌细胞侵袭。结论胶原对准剂和交联剂ASPN增加了ECM网络,减少了迁移,本初步研究为ASPN作为一种抗转移药物的应用提供了希望,经过大量动物实验的证实,并通过临床前试验取得了积极的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Tumor Biology
Tumor Biology 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
18
审稿时长
1 months
期刊介绍: Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression. Specific topics of interest include, but are not limited to: Pathway analyses, Non-coding RNAs, Circulating tumor cells, Liquid biopsies, Exosomes, Epigenetics, Cancer stem cells, Tumor immunology and immunotherapy, Tumor microenvironment, Targeted therapies, Therapy resistance Cancer genetics, Cancer risk screening. Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines. The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication. Tumor Biology is the Official Journal of the International Society of Oncology and BioMarkers (ISOBM).
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