1 Background

The digestive system is one of the most important systems in our body, and related tumours frequently occur [1]. Digestive system malignant tumours can be classified into oesophageal, gastric, small intestinal, colon, rectal, appendiceal, anal, hepatic and pancreatic cancer based on the organ from which the abnormal cell proliferation is derived [2]. These tumours cause adverse effects on the physical and mental health of high-risk individuals [3, 4]. According to the report released by the International Agency for Research on Cancer, for both sexes combined, four digestive system cancer types are in the top 10 cancer types for worldwide incidence (23.4% of total cases) and five are in the top 10 for worldwide mortality (35.6% of total cases) [5]. Due to the lack of typical early symptoms, early detection is often difficult and patients often miss the opportunity for optimal treatment [6, 7]. Although endoscopy, cholangiopancreatography and needle aspiration techniques have improved, the invasiveness, uncertainty of operation and high cost restrict large-scale screening [8, 9]. At present, serum carcinoembryonic antigen (CEA), Carbohydrate antigen 19–9 (CA19-9), and Carbohydrate antigen 125 (CA125) are normally used in clinical diagnosis, but both their sensitivity and specificity are low [30], and synaptotagmin 7 (SYT7) [31], have also been reported.

The contents of exosomes are complex and include microRNAs, circular RNAs, long noncoding RNAs (lncRNAs), DNA fragments, proteins, lipids and metabolites (Fig. 1) [32, 33]. These cargoes determine the function of exosomes to a great degree [34, 35]. Exosomes modulate the tissue microenvironment by mediating autocrine, juxtacrine and paracrine interactions, and they also participate in the suppression of antitumour immune responses, cancer angiogenesis, and tumour progression [36]. Exosome uptake by target cells is processed by lipid raft-mediated endocytosis, receptor-mediated endocytosis, phagocytosis, micropinocytosis and membrane fusion [37]. However, the detailed mechanisms remain unclear [32].

Exosomes need to be isolated from biological fluids for various studies [38,117]. In addition to TEX, cancer-associated fibroblast (CAF)-derived exosomes (CAF-exos) can also transmit microRNAs (miRNAs) to CRC. Recently, miR-135b-5p, which is transported by CAF-exos, was reported to downregulate thioredoxin-interacting protein (TXNIP) to promote angiogenesis [

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Abbreviations

AAT:

Antiangiogenic therapy

ADO:

Adenosine

ANGPT1:

Angiopoietin-1

ANGPT2:

Angiopoietin-2

ANGPTL7:

Angiopoietin-like 7

ANXA1:

Annexin A1

ARF6:

ADP ribosylation factor 6

BTG2:

B‐cell translocation gene 2

CA125:

Carbohydrate antigen 125

CA19-9:

Carbohydrate antigen 19–9

CAF:

Cancer-associated fibroblast

CEA:

Carcinoembryonic antigen

CLDN11:

Claudin-11

CLEC3B:

C-Type Lectin Domain Family 3 Member B

CNS:

Central nervous system

CRC:

Colorectal cancer

DACT2:

Disheveled binding antagonist of beta-catenin 2

Dkk-3:

Dickkopf-3

DPP4:

Dipeptidyl peptidase IV

EC:

Endothelial cell

ECM:

Extracellular matrix

ERG:

Erythroblast transformation specific (ETS) related gene

ESCC:

Oesophageal squamous cell carcinoma

ESCRT:

Endosomal sorting complex needed for transport

ESE:

Early-sorting endosome

FGF:

Fibroblast growth factor

FOXM1D:

Forkhead Box M1 D

Foxo:

Forkhead Box O

GC:

Gastric cancer

GDF15:

Growth/differentiation factor 15

GOLPH3:

Golgi phosphoprotein 3

GRP78:

Glucose-regulated protein 78

HCC:

Hepatocellular carcinoma

HGF:

Hepatocyte growth factor

HK2:

Hexokinase 2

HSCs:

Hepatic stellate cells

HUVECs:

Human umbilical vein endothelial cells

IA:

Intussusceptive angiogenesis

ILVs:

Intraluminal vesicle

IRE1:

Inositol- requiring enzyme 1 alpha

KIF14:

Kinesin family member 14

KLF12:

Krüppel-like factor 12

KLF2:

Krüppel-like factor 2

KLF4:

Krüppel-like factor 4

KRIT1:

Krev interaction trapped protein 1

LncRNAs:

Long noncoding RNAs

LOXL1–4:

Lysyl oxidase-like 1–4

LSE:

Late-sorting endosome

MLL3:

Histone-lysine N-methyltransferase-3

MMP:

Matrix metalloproteinase

MVBs:

Multivesicular bodies

NSF:

N-ethyl- maleimide-sensitive factor

PAR1:

Protease-activated receptor-1

PABPC1:

Poly (A) binding protein cytoplasmic 1

PC:

Pancreatic cancer

PDAC:

Pancreatic ductal adenocarcinoma

PDGF:

Platelet-derived growth factor

PKM2:

Pyruvate kinase M2

PLD2:

Phospholipase D2

PLGF:

Placental growth factor

PML:

Promyelocytic leukaemia

POSTN:

Periostin

PTEN:

Phosphatase and tensin homologue

SA:

Sprouting angiogenesis

sEVs:

Small extracellular vesicles

SNARE:

Soluble N-ethyl- maleimide-sensitive factor-attachment protein receptor complex

SNHG16:

Small nucleolar RNA host gene 16

SYT7:

Synaptotagmin 7

TAMs:

Tumour-associated macrophages

TEX:

Tumour-derived exosomes

TME:

Tumour microenvironment

TSP-1:

Thrombospondin-1

TXNIP:

Thioredoxin-interacting protein

VC:

Vessel co-option

VEGF-A:

Vascular endothelial growth factor A

VM:

Vascular mimicry

ZMYND11:

Zinc finger MYND-type containing 11

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Funding

This work was supported by National Natural Science Foundation of China (82203854, 82102702, 82103322), Key Research and Development Program of Shandong Province (No.2021CXGC011104; No.2019JZZY010104; No.2019GSF108146), Academic promotion programme of Shandong First Medical University (2019QL021), and Special Foundation for Taishan Scholars Program of Shandong Province (No.ts20190978), Natural Science Foundation of Shandong Province of China (ZR2020QH180, ZR2021QH141), Youth Innovation Science and Technology Program of Shandong Provincial Universities (2022KJ187), China postdoctoral science foundation (2022M711970), Clinical Medical Science and Technology Innovation Project of **an (202225046).

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Shandong Provincial Hospital, Shandong University, **an, 250021, Shandong, China

    Yuan Liu, Liang Shang & Le** Li

  2. Department of General Surgery, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Bei**g, 100730, China

    Hao Wu

  3. Department of Gastrointestinal Surgery, Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong Provincial Hospital, **an, 250021, China

    Yuan Liu, Yaodong Sang, Wei Chong, Liang Shang & Le** Li

  4. Department of Gastrointestinal Surgery, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, **an, 250021, China

    Yuan Liu, Yaodong Sang, Wei Chong, Liang Shang & Le** Li

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  1. Yuan Liu
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  2. Hao Wu
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  3. Yaodong Sang
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  4. Wei Chong
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  5. Liang Shang
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  6. Le** Li
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Contributions

YL and HW had the idea for the article, YL and HW performed the literature search and finished the manuscript; YL, WC and YDS finished the figures and tables; WC, LS and LPL made critical revisions and proofread the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Wei Chong, Liang Shang or Le** Li.

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Liu, Y., Wu, H., Sang, Y. et al. Research progress of exosomes in the angiogenesis of digestive system tumour. Discov Onc 15, 33 (2024). https://doi.org/10.1007/s12672-024-00879-4

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