Gastric cancer (GC) with peritoneal metastases and malignant ascites continues to have poor prognosis. Exosomes mediate intercellular communication during cancer progression and promote therapeutic resistance. Samsung Medical Center researchers report the significance of exosomes derived from malignant ascites (EXOAscites) in cancer progression and use modified exosomes as resources for cancer therapy. EXOAscites from patients with GC stimulated invasiveness and angiogenesis in an ex vivo three-dimensional autologous tumor spheroid microfluidic system. EXOAscites concentration increased invasiveness, and blockade of their secretion suppressed tumor progression. In MET-amplified GC, EXOAscites contain abundant MET; their selective delivery to tumor cells enhanced angiogenesis and invasiveness. Exosomal MET depletion substantially reduced invasiveness; an additive therapeutic effect was induced when combined with MET and/or VEGFR2 inhibition in a patient-derived MET-amplified GC model. Allogeneic MET-harboring exosome delivery induced invasion and angiogenesis in a MET non-amplified GC model. MET-amplified patient tissues showed higher exosome concentration than their adjacent normal tissues. Manipulating exosome content and production may be a promising complementary strategy against GC.
Conceptual use of exosome therapy as personalized medicine in GC
Schematic showing the potential of exosomes as biomarkers and for predicting the response to therapy. EXOAscites isolated from the ascites of patients with cancer (A and B) induced cancer invasion and angiogenesis (C). Scale bars, 500, 100, 50, and 25 μm. Specifically, MET contained in EXOAscites from MET-amplified cancer cells was a dose-dependent driver of tumor invasiveness and angiogenesis in both MET-amplified and non-amplified cells (D). Thus, MET in EXOAscites can be used as a biomarker for GC diagnosis and prognosis (D). A therapeutic strategy based on engineered exosomes to deplete MET or other therapeutically relevant proteins represents a promising avenue for precision medicine in GC (E).