Table Info

Table 1.

Key functions of exosomal TGF-β

Function of exosomal TGF-β	Mechanism	Resulting effect	Cancer type(s)	Reference(s)
Fibroblast differentiation and activation	Activates SMAD-dependent signaling upon internalization into fibroblasts.	Promotes differentiation of fibroblasts into CAFs, enhances CAF marker expression.	Prostate cancer, bladder cancer, gastric cancer, and lung adenocarcinoma.	[89–91, 103]
ECM remodeling	Enhances LOX activity, leading to collagen cross-linking.	Stiffens the ECM, creating a favorable environment for metastasis development.	General (tumor microenvironment).	[87, 103]
Angiogenesis promotion	Stimulates angiogenesis via myofibroblast phenotype.	Enhances tumor growth in vivo.	Prostate cancer.	[89]
MSC modulation	TGF-β interaction with receptors on MSCs.	Increases synthesis and release of pro-inflammatory IL-6, supporting metastasis via immunosuppression.	Osteosarcoma, chronic myeloid leukemia.	[92, 95, 96]
Non-coding RNA-mediated signaling	Delivery of circPAGRGL, miR-21-5p, miR-92, miR-142-3p, and miR-506-3p via exosomes.	Induces TGF-β expression, enhances cell proliferation and metastasis, promotes EMT, and supports phenotypic switch of neutrophils to pro-tumorigenic N2.	Colorectal cancer, gastric cancer, and lung cancer.	[93, 94, 100]
Premetastatic niche formation	Activation of TGF-β signaling in hepatic Kupffer cells and stellate cells.	Remodels liver tissue, making it more favorable for metastasis by stimulating fibronectin and collagen type I production.	Pancreatic ductal adenocarcinoma, lung cancer.	[98, 100]
EMT induction	Activation of SMAD2/3 signaling.	Promotes a more motile and invasive mesenchymal phenotype, enhancing migration and invasion.	General (ovarian cancer).	[104]
Immune suppression	Transfer of TGF-β1 to tumor-infiltrating natural killer cells.	Impairs NK cell functioning via TGF-β/SMAD pathway activation, supports immune evasion of quiescent cells.	Renal cell carcinoma.	[105]
Macrophage reprogramming	Stimulation of macrophage chemotaxis and reprogramming.	Promotes proangiogenic phenotype in macrophages, characterized by upregulation of proangiogenic factors.	Head and neck squamous cell carcinoma.	[80]

CAFs: cancer-associated fibroblasts; ECM: extracellular matrix; EMT: epithelial-mesenchymal transition; LOX: lysyl oxidase; MSC: mesenchymal stem cell; TGF-β: transforming growth factor-β

Declarations

Author contributions

TR: Conceptualization, Investigation, Project administration, Supervision, Visualization, Writing—original draft, Writing—review & editing. NP: Data curation, Investigation, Writing—original draft, Writing—review & editing.

Conflicts of interest

The authors report no conflicts of interest.

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