Exosomal Galectin-3 promotes peritoneal metastases in gastric adenocarcinoma via microenvironment alterations

被引：1

作者：

Fan, Yibo ^{[1
]}

Song, Shumei ^{[2
]}

Pizzi, Melissa Pool ^{[1
]}

Zou, Gengyi ^{[1
]}

Vykoukal, Jody V. ^{[3
]}

Yoshimura, Katsuhiro ^{[1
,4
]}

Jin, Jiankang ^{[1
]}

Calin, George A. ^{[5
]}

Waters, Rebecca E. ^{[6
]}

Gan, Qiong ^{[6
]}

Wang, Linghua ^{[7
]}

Hanash, Samir

Dhar, Shilpa S. ^{[1
]}

Ajani, Jaffer A. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Div Canc Med, Houston, TX 77030 USA

[2] Coriell Inst Med Res, Camden, NJ 08103 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA

[4] Hamamatsu Univ, Sch Med, Dept Tumor Pathol, Hamamatsu, Shizuoka 4313192, Japan

[5] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Div Pathol & Lab Med, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Div Pathol & Lab Med, Houston, TX 77030 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

来源：

ISCIENCE | 2025年 / 28卷 / 01期

基金：

美国国家卫生研究院;

关键词：

TO-MESENCHYMAL TRANSITION; NICHE FORMATION; CANCER; CELLS; EXPRESSION; PHENOTYPE; EVOLUTION; INITIATE;

D O I：

10.1016/j.isci.2024.111564

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Peritoneal carcinomatosis (PC) in gastric adenocarcinoma (GAC) is the most common metastatic site and leads to a short median survival. Exosomes have been shown to remodel the microenvironment, facilitating tumor metastases. However, the functional component in GAC cell-derived exosomes that remodel the landscape in the peritoneal cavity remains unclear. To address this, we performed in-depth proteomic profiling of ascites-derived exosomes from patients with PC, and we found that Galectin-3 was highly enriched in exosomes derived from malignant ascites. exosomal Galectin-3 was the crucial regulator of PC. Blockage of exosomal Galectin-3 significantly inhibited tumor metastases and prolonged overall survival. Exosomal Galectin-3 activated cancer-associated fibroblasts through integrin a1b1/FAK/Akt/mTOR/CXCL12 signaling. Combined inhibition of the CXCL12-CXCR4 axis and exosomal Galectin-3 enhanced the efficacy of anti-PD-1 immunotherapy, leading to significantly diminished PC progression and durable antitumor responses. These findings provide a rationale for clinical strategy of targeting exosomal Galectin-3 to treat PC.

引用

页数：22

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