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Exosomes in Cancer and Inflammatory Diseases

Exosomes and other EVs are associated with many aspects of cancer. Tumor cells secrete exosomes and other EVs containing messages related to tumor initiation, growth, progression, metastasis, and drug resistance.

The Multiple Roles of EVs in Cancer

Illustration showing the many roles of exosomes in cancer disease progression

Broadly, the role of exosomes and other EVs in cancer can be divided into four categories:

 

 

Figure adapted from Zhang, X., et al. (2015) Exosomes in cancer: small particle, big player. J Hematol Oncol 8, 83 (PMID: 26156517). License provided by CC License.

Exosomes Facilitate Tumor Growth and Metastasis

In cancer cells, exosomes and other EVs transport cargo that is implicated in each stage of tumor growth and metastasis. For instance, cancerous cells can secrete EVs containing growth factors that have multiple roles in tumor growth and metastasis, including the induction of epithelial-to-mesenchymal transition (EMT), the transformation of normal cells into malignant cells, and the increased stemness of cancer cells.

Additionally, oncogenic cells can secrete EVs containing anti-apoptotic factors, like Survivin, to prevent cell death, and growth factors, like VEGF, to increase angiogenesis in the tumor microenvironment (TME).

Read EMT and Stemness FAQs

 

Exosome Cargo Cancers Reported Outcome
KRAS
c-MET
MIF
EGFR/EGFRvIII
Colon, Melanoma, Pancreatic, Breast Inhibits apoptosis of tumor cells
Survivin Cervical, Breast, Lung Enhances angiogenesis and thrombosis
VEGF
Angiogenin
NSCLC, Renal, Colon, Glioblastoma Involved in epithelial to mesenchymal transition (EMT)
Vimentin
Rab3D
TGF-β
NSCLC, Prostate, Bladder, Colorectal, Breast, Gastric Induces myofibroblast differentiation
TGF-β
HIF-1α
c-KIT
Wnt3a
NSCLC, NPC, GIST, Diffuse large B cell lymphoma Enhancing tumor cell migration and invasion, establishing pre-metastatic niche, remodeling extra cellular matrix

NSCLC, Non small-cell lung cancer; NPC, Nasopharyngeal carcinoma; GIST, Gastrointestinal stromal tumor

 

Extracellular Vesicle-Mediated Immunosuppression

To be successful, tumors need to evade and suppress the immune response of the host. Some mechanisms of immunosuppression in the tumor microenvironment (TME) include cytotoxic inhibition of NK cells and effector T cells, expansion and activation of T regulatory (Treg) cells, and polarization of M2 macrophages. EVs including exosomes play an important role in each of these immunosuppressive processes.

Exosome Cargo Cancers Reported Outcome
NKG2D
DNAM-1
Galectin-9
PD-L1
FasL
CD39CD73
Ovarian, NPC Melanoma, Bladder, Colorectal, Prostate, Breast Inhibits cytotoxicity of NK cells and effector T cells

Promotes apoptosis of effector cells
HSP70 NSCLC, Renal, Breast, Colon Activates and expands myeloid-derived suppressor cells (MDSCs)
EGFR
TGF-β
CCL20
NSCLC, Melanoma, NPC Promotes expansion and function of regulatory T cells (Tregs)
EGFR NSCLC Inhibits dendritic cell (DC) differentiation

NSCLC, non-small cell lung cancer; NPC, nasopharyngeal carcinoma

Exosome-Mediated Resistance to Drug Therapy

In addition to tumor metastasis and immunosuppression, exosomes and other EVs can contribute to tumor growth and disease progression by directly promoting resistance to anti-cancer therapy. EVs can transfer material, such as multi-drug resistant (MDR)-associated proteins and miRNAs to susceptible cells, transforming them into therapy-resistant cells. Additionally, drugs and drug metabolites can be encapsulated within EVs to facilitate transport out of the tumor cell, rendering the drug ineffective. Finally, due to their expression of cell surface markers that are also targets for therapy, such as CD20Her-2, and PD-L1, EVs can serve as decoy targets, limiting therapeutic efficacy.

Exosomes and Other Extracellular Vesicles as Biomarkers for Cancer

In general, a biomarker is a biological characteristic that can be measured and monitored. Biomarkers are an especially useful tool for the diagnosis and monitoring of cancer when the primary tumor site is in a hard-to-reach place, such as the brain or other solid organ.

EVs are under investigation as biomarkers to:

  • diagnose disease,
  • determine disease burden, and
  • monitor disease progression and/or treatment efficacy.

Learn more about Bio-Techne's Exosome Platform for diagnostic biomarker discovery and development. 

Cancer  Exosome Markers
Colon VSIG3GPA33CD147
Ovarian CD147EpCAMCA125/MUC16
Breast EGFR
Pancreatic Glypican-1MIF
Lung CD151L1CAM/CD171Tetraspanin 8, (NSCLC-EGFRLRG-1)
Glioblastoma Syndecan-1EGFRvIII
Prostate PSAPSMAPTEN
Melanoma TRP2VLA-4HSP70PD-L1

 

Exosomes and other EVs are implicated in the pathogenesis of many inflammatory diseases including cardiovascular disease, kidney disease, autoimmune disorders, and viral infections. Thus far, much of this work has investigated the role of various microRNAs (miRNAs) and protein cargo, the role of exosomes in inflammatory disease is being increasingly studied.

Disease Exosome/EV Cargo
Cardiovascular Disease Cystatin CSerpin F2CD14PolyIg ReceptorC5aTissue FactorCD31CD62e
Renal Disease AQP1AQP2Aminopeptidase N
Systemic Lupus Erythematosus (SLE) IFN-αTNF-αC1qCD54
Type 1 Diabetes GAD65Proinsulin
HIV HMGB1NF-LHIV gp120