Exosomal microRNAs synergistically trigger stromal fibroblasts in breast cancer

被引：46

作者：

Scognamiglio, Iolanda ^{[1
]}

Cocca, Lorenza ^{[1
]}

Puoti, Ilaria ^{[1
]}

Palma, Francesco ^{[3
]}

Ingenito, Francesco ^{[3
]}

Quintavalle, Cristina ^{[2
]}

Affinito, Alessandra ^{[3
]}

Roscigno, Giuseppina ^{[3
]}

Nuzzo, Silvia ^{[4
]}

Chianese, Rosario Vincenzo ^{[1
]}

Belli, Stefania ^{[5
]}

Thomas, Guglielmo ^{[6
]}

Schomann, Timo ^{[3
,7
]}

Chan, Alan ^{[3
]}

Stoppelli, Maria Patrizia ^{[5
]}

Condorelli, Gerolama ^{[1
,2
]}

机构：

[1] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Via Pansini 5, I-80131 Naples, Italy

[2] Natl Res Council CNR, Inst Endocrinol & Expt Oncol G Salvatore IEOS, Via Pansini 5, I-80131 Naples, Italy

[3] Percuros BV, Eerbeeklaan 42, NL-2573 HT The Hague, Netherlands

[4] IRCCS SYNLAB SDN, Via Gianturco 113, I-80143 Naples, Italy

[5] Natl Res Council CNR, Inst Genet & Biophys IGB, Via Castellino 111, I-80131 Naples, Italy

[6] Mediterranea Cardioctr, Via Orazio 2, I-80122 Naples, Italy

[7] Leiden Univ, Med Ctr, Dept Radiol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2022年 / 28卷

关键词：

PROMOTE TUMOR-GROWTH; MATRIX METALLOPROTEINASE-1; ACTOMYOSIN CONTRACTILITY; CARCINOMA-CELLS; MICROENVIRONMENT; INVASION; DIFFERENTIATION; PROLIFERATION; METASTASIS; RESISTANCE;

D O I：

10.1016/j.omtn.2022.02.013

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. TNBC progression is sustained by recruitment of a strong tumor microenvironment (TME) mainly composed of cancer-associated fibroblasts (CAFs) able to endorse tumor hallmarks. Increasing evidences demonstrate that exosomes mediate the crosstalk between cancer cells and the TME. We examined TNBC-derived exosomes and their microRNA (miRNA) cargo in activation of normal fibroblasts (NFs) toward CAFs. We demonstrated that TNBC cell-derived exosomes increased NF collagen contraction and migration alongside CAF molecular markers. Exosome-activated fibroblasts promoted the invasion potential of normal breast epithelial cells, as assessed by an organotypic co-culture assay that resembled the in vivo context. We also investigated TNBC cell-derived exosome cargo in activating NFs to CAFs by performing small RNA sequencing. We found that the synergistic action of miR-185-5p, miR-652-5p, and miR-1246 boosted fibroblast migration and contraction, promoting specific CAF subspecialization toward a pro-migratory functional state. These data highlight the role of breast cancer cells in re-education of the TME and their contribution to tumor evolution.

引用

页码：17 / 31

页数：15

共 75 条

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