Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer.

Autor:	Hyung S; Precision Medicine Research Institute, Samsung Medical Center, Seoul, Republic of Korea.; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Ko J; Department of BioNano Technology, Gachon University, Gyeonggi 13120, Republic of Korea., Heo YJ; Neocella Inc., Irvine, CA 92606, USA., Blum SM; Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA 02114, USA., Kim ST; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Park SH; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Park JO; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Kang WK; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Lim HY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., Klempner SJ; Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA 02114, USA., Lee J; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2023 Nov 24; Vol. 9 (47), pp. eadk1098. Date of Electronic Publication: 2023 Nov 24.
DOI:	10.1126/sciadv.adk1098
Abstrakt:	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. Here, we report the significance of exosomes derived from malignant ascites (EXO Ascites ) in cancer progression and use modified exosomes as resources for cancer therapy. EXO Ascites from patients with GC stimulated invasiveness and angiogenesis in an ex vivo three-dimensional autologous tumor spheroid microfluidic system. EXO Ascites concentration increased invasiveness, and blockade of their secretion suppressed tumor progression. In MET -amplified GC, EXO Ascites 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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu