外泌体在肿瘤中的研究

应用：Therapy
外泌体特点
IL-2-containing tumor cell exosomes GE11- or EGFpositive 293 exosomes SMNC-EXOs
IFN-γ-Dex
内含物 IL-2
siRNA
受体
CTL, macrophages, NK cells, and B lymphocytes.
pancreatic cancer; 3. Double-stranded DNA in exosomes a novel biomarker in
cancer detection; 4. Exosomal long noncoding RNA CRNDE-h as a novel serum-
based biomarker for diagnosis and prognosis of colorectal cancer;
例：
• 1. Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis;
• 2. Exosomes Secreted under Hypoxia Enhance Invasiveness and Stemness of Prostate Cancer Cells by Targeting Adherens Junction Molecules;
Exosomes redirect metastatic distribution
Exosomal ITGs determine organotropism
Exosomal ITGs as organotropism biomarkers
胰腺癌早期诊断： Glypican-1 identifies cancer exosomes and detects early pancreatic cancer,nature,2015
• 5. Human tumor virus utilizes exosomes for intercellular communication;
• 6. Murine Mammary Carcinoma Exosomes Promote Tumor Growth by Suppression of NK Cell Function;
制 • 8.创新性想法提出
例：
1. Proteomic Analysis of Exosome-like Vesicles Derived from Breast Cancer Cells, ANTICANCER RESEARCH.
2. Clinical Impact of Serum Exosomal MicroRNA-21 As a Clinical Biomarker in Human Esophageal Squamous Cell Carcinoma, Cancer. 3. Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in
EGFR-expressing cancer tissues
Doxorubicin H22 cells
MHC-I
NK cells,
应用 In vivo/in vitro
In vivo/in vitro
In vivo/in vitro phase II clinical trial
例:
• 1. Exosomes derived from IL-12-anchored renal cancer cells increase induction of specific antitumor response in vitro; • 2. Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells; • 3. A phase I study of dexosome immunotherapy in patients with • advanced non-small cell lung cancer; • 4. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC;
• 4. MicroRNAs Transfer from Human Macrophages to HepatoCarcinoma Cells and Inhibit Proliferation;
癌细胞作为供体
癌种
Breast cancer pancreatic colon gastric lung ovarian bladder
应用：The novel biomarkers
来源
Blood； Urinary； Salivary；
内含物
蛋白； miRNA； long noncoding RNA DNA； DNA methylation；
标志
early pancreatic cancer； Sunitinib Resistance； Castration-resistant； Prognostic Markers ；
癌细胞状态
内含物
Normal
蛋白
EMT
miRNA
Hypoxia
lncRNA
Resistance
circRNA
Triple-negative breast DNA
cancer
more invasive
Cancer stem cells
Gene expression cells；
Virus；
Drug treated；
蛋白 miRNA lncRNA circRNA
效应
Proliferation； Resistance； migration； invasion； Angiogenesis； appoptosis; Differentiation;
经典文献：
• 1. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands;
Renal Cancer by Acting as a Competing Endogenous RNA, Cacner cell. 4. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver, NATURE CELL BIOLOGY； 5. Tumour exosome integrins determine organotropic metastasis, Nature;
• 3. Cancer Exosomes Trigger Fibroblast to Myofibroblast Differentiation;
• 4. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumorassociated macrophage infiltration and M2 polarization;
• 2. Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b;
• 3. Exosome Transfer from Stromal to Breast Cancer Cells Regulates Therapy Resistance Pathways;
经典文献:126-year-old “seed-and-soil” hypothesis
Future metastatic sites Uptake Exosomes
Exosomes redirect metastatic distribution
Organ-specific tumour exosomes interact with Resident cells.
外泌体在肿瘤研究中的应用
癌细胞作为受体
癌种
细胞种类
Breast cancer Macrophages；
pancreatic mesenchymal
colon
stromal cells；
gastric
Fibroblasts；
lung
Dendritic Cell;
ovarian
bladder
外泌体内含物
http://www.exosomedx.cபைடு நூலகம்m/patients
例:
1. Clinical Impact of Serum Exosomal MicroRNA-21 As a Clinical Biomarker in Human Esophageal Squamous Cell Carcinoma； 2. Glypican-1 identifies cancer exosomes and detects early
Levels of circulating GPC11 Exosomes inform pancreatic cancer resection outcome
Elisa
GPC11 crExos detect early PanIN lesions.
谢谢！
思路：
• 1.测序(蛋白/mRNA/miRNA/lncRNA/circRNA) • 2.测序(蛋白/mRNA/miRNA/lncRNA/circRNA)+临床验证 • 3.功能+测序(蛋白/mRNA/miRNA/lncRNA/circRNA) • 4.功能+简单信号通路 • 5.功能+蛋白/mRNA/miRNA/lncRNA/circRNA+下游机制 • 6.功能+蛋白/mRNA/miRNA/lncRNA/circRNA+上游调控 • 7.功能+蛋白/mRNA/miRNA/lncRNA/circRNA+上游调控+下游机
bone marrow progenitor；
效应
Proliferation； migration ； invasion ； Angiogenesis； Premetastatic Niche； appoptosis; Differentiation; Resistance； EMT; MET; Impair Lymphocyte;
效应细胞
nontumorigenic epithelial cells； Endothelial Cell ； NK Cell； MDSCs； Liver cells； Cancer cells； tumor-associated macrophage ； T cells； fibroblasts
MSC;
GPC1 is a specific marker of cancer exosomes
GPC11 circulating exosomes are a cancer biomarker.
GPC11 crExos contain oncogenic KRASG12D.
GPC11 crExos detect early pancreatic cancer