Human pancreatic cancer cell exosomes, but not human normal cell exosomes, act as an initiator in cell transformation

Author:

Stefanius Karoliina12ORCID,Servage Kelly12ORCID,de Souza Santos Marcela1,Gray Hillery Fields12,Toombs Jason E3,Chimalapati Suneeta12,Kim Min S4,Malladi Venkat S4,Brekken Rolf35ORCID,Orth Kim126ORCID

Affiliation:

1. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States

2. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States

3. Division of Surgical Oncology, Department of Surgery, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, United States

4. Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, United States

5. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States

6. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States

Abstract

Cancer evolves through a multistep process that occurs by the temporal accumulation of genetic mutations. Tumor-derived exosomes are emerging contributors to tumorigenesis. To understand how exosomes might contribute to cell transformation, we utilized the classic two-step NIH/3T3 cell transformation assay and observed that exosomes isolated from pancreatic cancer cells, but not normal human cells, can initiate malignant cell transformation and these transformed cells formed tumors in vivo. However, cancer cell exosomes are unable to transform cells alone or to act as a promoter of cell transformation. Utilizing proteomics and exome sequencing, we discovered cancer cell exosomes act as an initiator by inducing random mutations in recipient cells. Cells from the pool of randomly mutated cells are driven to transformation by a classic promoter resulting in foci, each of which encode a unique genetic profile. Our studies describe a novel molecular understanding of how cancer cell exosomes contribute to cell transformation.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that major issues remain unresolved (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

Funder

National Institutes of Health

Once Upon A Time Foundation

Welch Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Cited by 76 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3