Role of stromal activin A in human pancreatic cancer and metastasis in mice

被引：20

作者：

Mancinelli, Georgina ^{[1
]}

Torres, Carolina ^{[1
]}

Krett, Nancy ^{[2
]}

Bauer, Jessica ^{[2
]}

Castellanos, Karla ^{[1
]}

McKinney, Ron ^{[1
]}

Dawson, David ^{[3
]}

Guzman, Grace ^{[4
]}

Hwang, Rosa ^{[5
]}

Grimaldo, Sam ^{[6
]}

Grippo, Paul ^{[1
]}

Jung, Barbara ^{[2
]}

机构：

[1] Univ Illinois, Dept Med, Div Gastroenterol & Hepatol, Chicago, IL USA

[2] Univ Washington, Dept Med, Coll Med, 1959 NE Pacific St,RR-512,Box 356020, Seattle, WA 98195 USA

[3] UCLA Med Ctr, Ronald Reagan UCLA Med Ctr, Santa Monica, CA USA

[4] Univ Illinois, Dept Pathol, Chicago, IL USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Breast Surg Oncol, Div Surg, Houston, TX 77030 USA

[6] Univ Illinois, Dept Surg, Chicago, IL 60680 USA

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

基金：

美国国家卫生研究院;

关键词：

THERAPEUTIC TARGETS; BREAST-CANCER; TUMOR; CELL; ADENOCARCINOMA; PROLIFERATION; SOTATERCEPT; PROGRESSION; SURVIVAL; ANEMIA;

D O I：

10.1038/s41598-021-87213-y

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：

Pancreatic ductal adenocarcinoma (PDAC) has extensive stromal involvement and remains one of the cancers with the highest mortality rates. Activin A has been implicated in colon cancer and its stroma but its role in the stroma of PDAC has not been elucidated. Activin A expression in cancer and stroma was assessed in human PDAC tissue microarrays (TMA). Activin A expression in human TMA is significantly higher in cancer samples, with expression in stroma correlated with shorter survival. Cultured pancreatic stellate cells (PSC) were found to secrete high levels of activin A resulting in PDAC cell migration that is abolished by anti-activin A neutralizing antibody. KPC mice treated with anti-activin A neutralizing antibody were evaluated for tumors, lesions and metastases quantified by immunohistochemistry. KPC mice with increased tumor burden express high plasma activin A. Treating KPC mice with an activin A neutralizing antibody does not reduce primary tumor size but decreases tumor metastases. From these data we conclude that PDAC patients with high activin A expression in stroma have a worse prognosis. PSCs secrete activin A, promoting increased PDAC migration. Inhibition of activin A in mice decreased metastases. Hence, stroma-rich PDAC patients might benefit from activin A inhibition.

引用

页数：13

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