ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment

被引：44

作者：

Au-Yeung, Chi-Lam ^{[1
,2
]}

Yeung, Tsz-Lun ^{[1
,2
]}

Achreja, Abhinav ^{[3
]}

Zhao, Hongyun ^{[3
]}

Yip, Kay-Pong ^{[4
]}

Kwan, Suet-Ying ^{[1
]}

Onstad, Michaela ^{[1
]}

Sheng, Jianting ^{[5
,6
]}

Zhu, Ying ^{[5
,6
]}

Baluya, Dodge L. ^{[7
]}

Co, Ngai-Na ^{[1
]}

Rynne-Vidal, Angela ^{[1
]}

Schmandt, Rosemarie ^{[1
,2
]}

Anderson, Matthew L. ^{[8
]}

Lu, Karen H. ^{[1
,2
]}

Wong, Stephen T. C. ^{[5
,6
]}

Nagrath, Deepak ^{[3
]}

Mok, Samuel C. ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, UTHlth Grad Sch Biomed Sci Houston, Houston, TX 77030 USA

[3] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA

[4] Univ S Florida, Dept Mol Pharmacol & Physiol, Tampa, FL 33620 USA

[5] Weill Cornell Med, Dept Syst Med & Bioengn, Houston Methodist Res Inst, Houston, TX 77030 USA

[6] Houston Methodist Canc Ctr, Ctr Precis Oncol, Houston, TX 77030 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Imaging Intervent Radiol, Houston, TX 77030 USA

[8] Baylor Coll Med, Duncan L Comprehens Canc Ctr, Dept Obstet & Gynecol, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

美国国家卫生研究院;

关键词：

OVERWEIGHT; OMENTIN-1; ADIPOKINE; INSULIN;

D O I：

10.1038/s41467-020-17383-2

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：

Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin's effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression. Advanced ovarian cancer usually spreads to the omentum. Here, the authors show that circulating intelectin-1 (ITLN1) has prognostic significance in patients with advanced ovarian cancer, and that mesothelial cell-derived ITLN1 in the omental tumor microenvironment suppresses ovarian cancer progression.

引用

页数：16

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