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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article numbere0222083
JournalPloS one
Volume14
Issue number9
DOIs
StatePublished - Jan 1 2019

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Epithelial-Mesenchymal Transition
transforming growth factor beta
cell movement
Transforming Growth Factor beta
carcinoma
Cell Movement
Genes
Cells
Tumors
genes
Self Tolerance
pancreatic neoplasms
Neoplasms
neoplasms
antigen-presenting cells
Immune system
surface antigens
Snails
Antigen-Presenting Cells
Surface Antigens

ASJC Scopus subject areas

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

Cite this

B7-1 drives TGF-β stimulated pancreatic carcinoma cell migration and expression of EMT target genes. / Kang, Jeong Han; Jung, Mi Yeon; Leof, Edward B.

In: PloS one, Vol. 14, No. 9, e0222083, 01.01.2019.

Research output: Contribution to journalArticle

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