B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes

Jeong Han Kang; Mi Yeon Jung; Edward B. Leof

doi:10.1371/journal.pone.0222083

B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes

Jeong Han Kang, Mi Yeon Jung, Edward B. Leof

Pulmonary and Critical Care Medicine

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

B7-1 proteins are routinely expressed on the surface of antigen presenting cells (APC) and within the innate immune system. They function to establish a biologically optimal and dynamic balance between immune activation and inhibition or self-tolerance. Interactions between B7-1 and its receptors, which include CD28, CTLA4 and PD-L1, contribute to both stimulatory as well as inhibitory or homeostatic regulation. In the current study, we investigated whether the tumor-promoting actions of transforming growth factor beta (TGF-β) disrupted this equilibrium in pancreatic cancer to promote malignant progression and an enhanced means to evade immune detection. The data show that B7-1 is (i) upregulated following treatment of pancreatic carcinoma cells with TGF-β; (ii) induced by TGF-β via both Smad2/3-dependent and independent pathways; (iii) required for pancreatic tumor cell in vitro migration/invasion; and (iv) necessary for TGF-β regulated epithelial-mesenchymal transition (EMT) through induction of Snail family members. Results from the proposed studies provide valuable insights into mechanisms whereby TGF-β regulates both the innate immune response and intrinsic properties of pancreatic tumor growth.

Original language	English (US)
Article number	e0222083
Journal	PloS one
Volume	14
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0222083
State	Published - Sep 1 2019

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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title = "B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes",

abstract = "B7-1 proteins are routinely expressed on the surface of antigen presenting cells (APC) and within the innate immune system. They function to establish a biologically optimal and dynamic balance between immune activation and inhibition or self-tolerance. Interactions between B7-1 and its receptors, which include CD28, CTLA4 and PD-L1, contribute to both stimulatory as well as inhibitory or homeostatic regulation. In the current study, we investigated whether the tumor-promoting actions of transforming growth factor beta (TGF-β) disrupted this equilibrium in pancreatic cancer to promote malignant progression and an enhanced means to evade immune detection. The data show that B7-1 is (i) upregulated following treatment of pancreatic carcinoma cells with TGF-β; (ii) induced by TGF-β via both Smad2/3-dependent and independent pathways; (iii) required for pancreatic tumor cell in vitro migration/invasion; and (iv) necessary for TGF-β regulated epithelial-mesenchymal transition (EMT) through induction of Snail family members. Results from the proposed studies provide valuable insights into mechanisms whereby TGF-β regulates both the innate immune response and intrinsic properties of pancreatic tumor growth.",

author = "Kang, {Jeong Han} and Jung, {Mi Yeon} and Leof, {Edward B.}",

note = "Funding Information: This work was supported by Public Health Service grants GM-55816 and GM-54200 from the National Institute of General Medical Sciences and the Mayo Foundation to E.B.L. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2019 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes

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