3D Cellular Architecture Affects MicroRNA and Protein Cargo of Extracellular Vesicles

被引：93

作者：

Rocha, Sara ^{[1
,2
,3
]}

Carvalho, Joana ^{[1
,2
]}

Oliveira, Patricia ^{[1
,2
]}

Voglstaetter, Maren ^{[4
]}

Schvartz, Domitille ^{[5
]}

Thomsen, Andreas R. ^{[6
,7
,8
]}

Walter, Nadia ^{[5
]}

Khanduri, Richa ^{[4
]}

Sanchez, Jean-Charles ^{[5
]}

Keller, Andreas ^{[9
]}

Oliveira, Carla ^{[1
,2
,10
]}

Nazarenko, Irina ^{[4
,7
,8
]}

机构：

[1] Univ Porto, I3S Inst Invest & Inovacao Saude, Rua Alfredo Allen 208, P-4200135 Porto, Portugal

[2] Univ Porto, Ipatimup Inst Mol Pathol & Immunol, Rua Julio Amaral de Carvalho 45, P-4200135 Porto, Portugal

[3] Univ Porto, ICBAS Inst Ciencias Biomed Abel Salazar, R Jorge Viterbo Ferreira 228, P-4050313 Porto, Portugal

[4] Univ Freiburg, Inst Infect Prevent & Hosp Epidemiol, Med Ctr, Fac Med, Breisacherstr 115b, D-79106 Freiburg, Germany

[5] Ctr Med Univ Geneva, Dept Human Prot Sci, Rue Michel Servet 1, CH-1211 Geneva, Switzerland

[6] Univ Freiburg, Med Ctr, Dept Radiat Oncol, Hugstaetterstr 55, D-79106 Freiburg, Germany

[7] German Canc Consortium DKTK, Partner Site Freiburg, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[8] German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[9] Saarland Univ, Univ Hosp, Clin Bioinformat, Kirrberger Str,Bldg E2-1, D-66123 Saarbrucken, Germany

[10] Univ Porto, Fac Med, Dept Pathol & Oncol, Alameda Prof Hernani Monteiro, P-4200319 Porto, Portugal

来源：

ADVANCED SCIENCE | 2019年 / 6卷 / 04期

关键词：

3D cell culture; cancer; extracellular vesicles; integrative network analysis; microwell arrays; MELANOMA-CELLS; 3-DIMENSIONAL CULTURE; ENRICHMENT ANALYSIS; CANCER EXOSOMES; GENE-EXPRESSION; IN-VIVO; TUMOR; TISSUE; REVEALS; GROWTH;

D O I：

10.1002/advs.201800948

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The success of malignant tumors is conditioned by the intercellular communication between tumor cells and their microenvironment, with extracellular vesicles (EVs) acting as main mediators. While the value of 3D conditions to study tumor cells is well established, the impact of cellular architecture on EV content and function is not investigated yet. Here, a recently developed 3D cell culture microwell array is adapted for EV production and a comprehensive comparative analysis of biochemical features, RNA and proteomic profiles of EVs secreted by 2D vs 3D cultures of gastric cancer cells, is performed. 3D cultures are significantly more efficient in producing EVs than 2D cultures. Global upregulation of microRNAs and downregulation of proteins in 3D are observed, indicating their dynamic coregulation in response to cellular architecture, with the ADP-ribosylation factor 6 signaling pathway significantly downregulated in 3D EVs. The data strengthen the biological relevance of cellular architecture for production and cargo of EVs.

引用

页数：17

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