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Molecular actions of exosomes and their theragnostics in colorectal cancer: current findings and limitations

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Abstract

Extracellular vesicles (EVs) are cell-released, membranous structures essential for intercellular communication. The biochemical compositions and physiological impacts of exosomes, lipid-bound, endosomal origin EVs, have been focused on, especially on the tumor-host interactions in a defined tumor microenvironment (TME). Despite recent progress in targeted therapy and cancer immunotherapy in colorectal cancer (CRC), cancer patients still suffer from distal metastasis and tumor relapse, suggesting unmet needs for biomarkers directing therapeutic interventions and predicting treatment responsiveness. As exosomes are indispensable for intercellular communication and high exosome abundance makes them feasible biomarker molecules, this review discusses exosome heterogeneity and how exosomes orchestrate the interplay among tumor cells, cancer stem cells (CSCs) and host cells, including stromal cells, endothelial cells and immunocytes, in the CRC TME. This review also discusses mechanisms for loading exosomal contents and potential exosomal DNA, RNA and protein biomarkers for early CRC detection. Finally, we summarize the diagnostic and therapeutic exosomes in clinical trials. We envision that detecting and targeting cancer-specific exosomes could provide therapeutic advances in developing personalized cancer medicine.

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Abbreviations

CAFs:

Cancer-associated fibroblasts

CEA:

Carcinoembryonic antigen

ceRNA:

Endogenous RNA

circRNAs:

Circular RNAs

CRC:

Colorectal cancer

CRCSCs:

Colorectal cancer stem cells

CSCs:

Cancer stem cells

CTC:

Circulating tumor cells

DCs:

Dendritic cells

ECM:

Extracellular matrix

EMT:

Epithelial-mesenchymal transition

ESCRT:

Endosomal sorting complexes required for transport

EVs:

Extracellular vesicles

FOBT:

Fecal occult blood test

HDI:

High developing index

HLECs:

Human lymphatic endothelial cells

HMEC-1:

Human microvascular endothelial cells

HUVECs:

Human umbilical vein endothelial cells

ILVs:

Intraluminal vesicles

LPS:

Lipopolysaccharide

MDSCs:

Myeloid-derived suppressor cells

MIIC:

Major histocompatibility complex class II-enriched component

MISEVs:

Minimal information for studies of extracellular vesicles

MN:

Micronuclei

mtDNA:

Mitochondria DNA

MVBs:

Multivesicular bodies

nSMase:

Neutral sphingomyelinase

SCD:

Symmetric cell division

SEER:

Surveillance, Epidemiology, and End Results

SLNs:

Sentinel lymph nodes

TGF-β1:

Transforming growth factor-β1

TME:

Tumor microenvironment

TRAF3:

TNF receptor-associated Factor 3

Tregs:

Regulatory T cells

VEGF:

Vascular endothelial growth factor

WHO:

World Health Organization

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Acknowledgements

This work was supported by the Cancer Progression Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) and YEN TJING LAING MEDICAL FOUNDATION in Taiwan.

Funding

Ministry of Science and Technology (109–2320-B-010–021 and 111–2628-B-A49-017 to W-L.H., 109–2314-B-075–081-MY3 to H-W. T., 109–2314-B-075–026 to C–C.L.); a grant from the Yen Tjing Ling Medical Foundation (CI-111–15 to W-L.H.), a grant from the Ministry of Health and Welfare, Center of Excellence for Cancer Research (MOHW107-TDU-B-211–114019, 111 W31208 to W-L.H.) and a grant from the Higher Education Sprout Project by the Ministry of Education (MOE) (110AC-D303 to W-L.H.). Taipei Veterans General Hospital (V111C-069 and V110C-189 to H-W.T.). The Innovative Research Grant of the National Health Research Institutes of Taiwan (NHRI-EX110-11010BI to W–H.Y.) and Ying Tsai Young Scholar Award (CMU108-YTY-04 to W–H.Y.).

Author information

Author notes

  1. Wen-Chun Lin and Chun-Chi Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nong Street, Taipei, 112, Taiwan

    Wen-Chun Lin, Yuh-Ching Twu & Wei-Lun Hwang

  2. Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, 112, Taipei, Taiwan

    Chun-Chi Lin

  3. Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan

    Chun-Chi Lin

  4. Division of Pathology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, 24352, Taiwan

    Yen-Yu Lin

  5. Graduate Institute of Biomedical Sciences, Research Center for Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, 406, Taiwan

    Wen-Hao Yang

  6. Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, 112, No. 201, Sec 2, Shipai Road, Taipei, Taiwan

    Hao-Wei Teng

  7. School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan

    Hao-Wei Teng

  8. Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan

    Wei-Lun Hwang

Authors
  1. Wen-Chun Lin
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  2. Chun-Chi Lin
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  3. Yen-Yu Lin
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  4. Wen-Hao Yang
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  5. Yuh-Ching Twu
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  6. Hao-Wei Teng
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  7. Wei-Lun Hwang
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Contributions

W–C.L., C–C.L. Y-Y.L., H-W.T. and W-L.H. wrote and revised the manuscript with assistance from W–H.Y. and Y-C.T.

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Correspondence to Hao-Wei Teng or Wei-Lun Hwang.

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Lin, WC., Lin, CC., Lin, YY. et al. Molecular actions of exosomes and their theragnostics in colorectal cancer: current findings and limitations. Cell Oncol. 45, 1043–1052 (2022). https://doi.org/10.1007/s13402-022-00711-7

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