Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication
Abstract
:1. Introduction
2. Effects of EVs and Their Cargo Molecules on Pancreatic Cancer
2.1. RNA Cargo in PCC-Derived EVs
2.1.1. MiRNA-23b-3p and miRNA-222
2.1.2. MiRNA-155 and ROS Detoxification Genes
2.1.3. MiRNA-194-5p
2.1.4. Circ-PDE8A
2.1.5. LncRNAs
2.2. Protein Cargo in PCC-Derived EVs
2.2.1. AEP
2.2.2. ANXA1
2.2.3. EphA2
2.2.4. Lin28B
2.2.5. ZIP4
2.3. RNA Cargo in EVs from PSCs and CAFs
2.3.1. MiRNA-10a-5p
2.3.2. MiRNA-21 and miRNA-221
2.3.3. MiRNA-106-5p
2.3.4. MiRNA-5703
2.3.5. SNAI1
2.4. RNA Cargo in EVs from TAMs and NKCs
2.4.1. MiRNA-365
2.4.2. MiRNA-501-3p
2.4.3. LncRNA-SBF2-AS1
2.5. RNA Cargo in EVs from CSCs
MiRNA-210
Cargo | Source of EVs | Type of Study | Major Function of Cargo Molecules | Ref. |
---|---|---|---|---|
miRNAs | ||||
miRNA-10a-5p | CAFs isolated from human pancreatic cancer tissues | In vitro | Support the aggressiveness of PANC-1 and SW1990 cells | [64] |
miRNA-21 | PSCs (human PSC21-S/T cell line), CAFs (human CAF-19 cell line) | In vitro | Reinforce the proliferation, migration and EMT process of PANC-1 and SUIT-2 cells; augment clonogenicity and sphere formation of Colo-357 cells | [66,67] |
miRNA-23b-3p | PCCs (human PANC-1 cells) | In vitro | Increase the proliferation, migration and invasion of PANC-1 cells | [11] |
miRNA-106-5p | CAFs isolated from human pancreatic cancer tissues | In vitro | Confer gemcitabine resistance in AsPC-1 cells | [68] |
miRNA-155 | PCCs (gemcitabine-treated human MIAPaCa-2 and Colo-357 cells, gemcitabine-resistant human PANC-1 cells) | In vitro, In vivo | Inhibit gemcitabine-induced apoptosis in MIAPaCa-2 and Colo-357 cells in vitro; confer gemcitabine resistance in PANC-1 cells in vivo | [15,16] |
miRNA-194-5p | Irradiated human PANC-1 and SW1990 cells | In vitro, In vivo | Augment the survival of SW1990 cells following radiation in vitro | [20] |
miRNA-210 | CSCs derived from gemcitabine-resistant human BxPC-3 cells | In vitro, In vivo | Inhibit gemcitabine-induced apoptosis in BxPC-3 and PANC-1 cells in vitro; confer gemcitabine resistance in BxPC-3 cells in vivo | [88] |
miRNA-221 | CAFs (human CAF-19 cell line), PSCs isolated from human pancreatic cancer tissues | In vitro | Stimulate the clonogenicity and sphere formation of Colo-357 cells | [66] |
miRNA-222 | PCCs (human Hs 766 T-L3 cells) | In vitro, In vivo | Enhance the proliferation, migration and invasion of CAPAN-1 and Hs 766 T-L3 cells in vitro; promote cancer progression in vivo | [12] |
miRNA-365 | TAMs (M2-polarized murine peritoneal macrophages) | In vitro, In vivo | Attenuate the gemcitabine efficacy in K989 murine cells | [76] |
miRNA-501-3p | TAMs (M2-polarized human THP-1 cells) | In vitro, In vivo | Enhance the migration and invasion of PANC-1 and BxPC-3 cells in vitro; promote cancer growth and metastasis in vivo | [80] |
miRNA-5703 | PSCs isolated from human pancreatic cancer tissues | In vitro | Promote the proliferation of Patu8988 and T3M4 cells | [73] |
Other non-coding RNAs | ||||
Circ-PDE8A | PCCs (human Hs 766 T-L2 cells) | In vitro, In vivo | Facilitate the invasion of BxPC-3 and CAPAN-1 cells in vitro; enhance liver metastasis in vivo | [24] |
LncRNA-HULC | PCCs (human PANC-1 cells) | In vitro, In vivo | Trigger migration, invasion and EMT process in PANC-1 and MIAPaCa-2 cells in vitro; promote cancer progression in vivo | [30] |
LncRNA-SBF2-AS1 | TAMs (M2-polarized human THP-1 cells) | In vitro, In vivo | Enhance the proliferation, migration and invasion of PANC-1 cells in vitro; force the tumorigenic ability of PANC-1 cells in vivo | [81] |
LncRNA-SOX2OT | PCCs (human Hs 766 T and Hs 766 T-L2 cells) | In vitro, In vivo | Promote EMT and stemness in Hs 766 T cells in vitro; trigger EMT, stemness and metastasis in vivo | [33] |
mRNAs | ||||
CAT and SOD2 | PCCs (gemcitabine-treated human MIAPaCa-2 and Colo-357 cells) | In vitro | Protect cell death induced by ROS in gemcitabine-treated MIAPaCa-2 cells | [16] |
SNAI1 | CAFs isolated from human pancreatic cancer tissues | In vitro | Promote the proliferation and gemcitabine resistance in AsPC-1 cells | [75] |
Proteins | ||||
AEP | PCCs (human BxPC-3 cells) | In vitro | Aggravate the invasion ability of BxPC-3 and AsPC-1 cells | [38] |
ANXA1 | PCCs (human MIAPaCa-2 cells) | In vitro | Facilitate the EMT, migration and invasion in MIAPaCa-2 cells | [43] |
EphA2 | PCCs (gemcitabine-resistant human PANC-1 cells) | In vitro | Develop gemcitabine resistance in MIAPaCa-2 and BxPC-3 cells | [48] |
Lin28B | PCCs (human PANC-1 and MIAPaCa-2 cells) | In vitro, In vivo | Increase the levels of PDGF in PANC-1 and MIAPaCa-2 cells, ultimately enhancing PSCs recruitment to the metastatic site | [52] |
ZIP4 | PCCs (hamster PC-1.0 cells) | In vitro, In vivo | Promote the proliferation and migration of PC-1.0 cells in vitro; enhance the growth of cancer in vivo | [59] |
3. Effects of PCC-Derived EVs on the Cellular Components in Pancreatic Cancer Microenvironment and Metastatic Site
3.1. Regulation of Endothelial Cells by PCC-Derived EVs
3.1.1. MiRNA-27a
3.1.2. Circ-IARS
3.1.3. ANXA1
3.1.4. Myoferlin
3.1.5. Tissue Factor
3.2. Regulation of Fibroblasts and Stellate Cells by PCC-Derived EVs
3.2.1. MiRNA-155
3.2.2. Podocalyxin
3.2.3. MiRNA-1290
3.3. Effects of PCC-derived EVs on Kupffer Cells
MIF
3.4. Effects of PCC-Derived EVs on Macrophages
3.4.1. MiRNA-301a
3.4.2. Ezrin
3.4.3. KRAS G12D
3.5. Effects of PCC-Derived EVs on Dendritic Cells
3.5.1. MiRNA-203
3.5.2. MiRNA-212-3p
Cargo | Source of EVs | Type of Study | Major Function of Cargo Molecules | Ref. |
---|---|---|---|---|
miRNAs | ||||
miRNA-27a | PCCs (human PANC-1 cells) | In vitro, In vivo | Enhance the proliferation, invasion and survival of human endothelial cells in vitro; promote cancer growth and angiogenesis in vivo | [91] |
miRNA-155 | PCCs (human BxPC-3 and SW1990 cells) | In vitro | Participate in the conversion from primary mouse fibroblasts to CAFs phenotypes | [110] |
miRNA-203 | PCCs (human PANC-1 cells) | In vitro | Interrupt the maturation of human dendritic cells | [133] |
miRNA-212-3p | PCCs (human PANC-1 cells) | In vitro | Repress the levels of MHC class II in human dendritic cells | [134] |
miRNA-301a | Hypoxic PCCs (human PANC-1 cells) | In vitro, In vivo | Convert human bone marrow–derived macrophages into M2 types in vitro; facilitate lung metastasis in vivo | [125] |
miRNA-1290 | PCCs (human PANC-1 cells) | In vitro | Activate human primary stellate cells; induce fibrogenic genes | [118] |
Non-coding RNA | ||||
Circ-IARS | PCCs (human Hs 766 T and Hs 766 T-L2 cells) | In vitro, In vivo | Disrupt the barrier integrity of human endothelial cells in vitro; promote invasion and metastasis in vivo | [97] |
Proteins | ||||
ANXA1 | PCCs (human MIAPaCa-2 cells) | In vitro | Mediate VEGF-induced migration and formation of the tube structure in human endothelial cells | [43] |
Ezrin | PCCs (PC080 and PC084 cells derived from human pancreatic cancer tissues) | In vitro, In vivo | Promote M2 polarization of THP-1/U937-derived macrophages in vitro; facilitate liver metastasis along with a high M2/M1 ratio in vivo | [128] |
KRAS G12D | Ferroptotic dying PCCs (human PANC-1 and AsPC-1 cells, primary PCCs from human pancreatic cancer tissues) | In vitro, In vivo | Promote M2 polarization of human mononuclear cell-derived macrophages in vitro; macrophage-mediated cancer growth is retarded by blocking KRAS G12D release and uptake in vivo | [130] |
MIF | PCCs (murine PAN02 cells) | In vitro, In vivo | Activate human Kupffer cells in vitro; enhance the formation of liver pre-metastatic niche in vivo | [120] |
Myoferlin | PCCs (human BxPC-3 cells) | In vitro | Enhance the proliferation and migration of human endothelial cells | [104] |
Podocalyxin | PCCs isolated from human pancreatic cancer tissues | In vitro | Contribute to the generation of pro-invasive niche via regulating the migration of immortalized human dermal fibroblasts | [115] |
Tissue Factor | PCCs (human BxPC-3 and CAPAN-1 cells) | In vitro | Activate human endothelial cells by upregulating E-selectin and IL-8 levels in a PAR-1 dependent manner | [109] |
4. Interference with EV-Based Conversation between Cells: Possibilities for Pancreatic Cancer Therapy
4.1. Cellular Factors Affecting EVs Biogenesis and Secretion
4.1.1. ANXA1
4.1.2. GIPC
4.1.3. PAFR
4.1.4. PAR2
4.1.5. RAB27
4.1.6. SMPD3
4.1.7. MiRNA-155 and lncRNA-PVT1
4.1.8. Other Possible Factors and Their Inhibitors
4.2. Regulation of EVs Uptake
4.2.1. AGER
4.2.2. ANXA6
4.2.3. TSPAN8
4.2.4. Dynamin-Dependent Endocytosis
4.2.5. Macropinocytosis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Moeng, S.; Son, S.W.; Lee, J.S.; Lee, H.Y.; Kim, T.H.; Choi, S.Y.; Kuh, H.J.; Park, J.K. Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication. Biomedicines 2020, 8, 267. https://doi.org/10.3390/biomedicines8080267
Moeng S, Son SW, Lee JS, Lee HY, Kim TH, Choi SY, Kuh HJ, Park JK. Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication. Biomedicines. 2020; 8(8):267. https://doi.org/10.3390/biomedicines8080267
Chicago/Turabian StyleMoeng, Sokviseth, Seung Wan Son, Jong Sun Lee, Han Yeoung Lee, Tae Hee Kim, Soo Young Choi, Hyo Jeong Kuh, and Jong Kook Park. 2020. "Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication" Biomedicines 8, no. 8: 267. https://doi.org/10.3390/biomedicines8080267