이지연 (성균관대학교 의과대학, 삼성서울병원) | 한빛사논문 > 한빛사

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성균관대학교 의과대학, 삼성서울병원

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Sci. Adv., Nov 24 2023, 9 (47) | https://doi.org/10.1126/sciadv.adk1098 Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer

Sujin Hyung ^1,2†, Jihoon Ko ^3†, You Jeong Heo ⁴, Steven M Blum ⁵, Seung Tae Kim², Se Hoon Park ², Joon Oh Park ², Won Ki Kang ², Ho Yeong Lim ², Samuel J Klempner^5*, Jeeyun Lee ^2*

¹Precision Medicine Research Institute, Samsung Medical Center, Seoul, Republic of Korea.

²Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

³Department of BioNano Technology, Gachon University, Gyeonggi 13120, Republic of Korea.

⁴Neocella Inc., Irvine, CA 92606, USA.

⁵Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.

^*Corresponding authors: J.L.; S.J.K.

^†These authors contributed equally to this work.

Abstract

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.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-27)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오소재

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