Blockade of stromal Gas6 alters cancer cell plasticity, activates NK cells and inhibits pancreatic cancer metastasis



Ireland, Lucy, Luckett, Teifion, Schmid, Michael C and Mielgo, Ainhoa ORCID: 0000-0002-4159-5931
(2019) Blockade of stromal Gas6 alters cancer cell plasticity, activates NK cells and inhibits pancreatic cancer metastasis. bioArXiv. 732149-.

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Abstract

<jats:title>Abstract</jats:title><jats:p>Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest cancers due to its aggressive and metastatic nature. PDA is characterized by a rich tumor stroma with abundant macrophages, fibroblasts and collagen deposition that can represent up to 90% of the tumor mass. Activation of the tyrosine kinase receptor AXL and expression of its ligand growth arrest-specific protein 6 (Gas6) correlate with a poor prognosis and increased metastasis in pancreatic cancer patients. Gas6 is a multifunctional protein that can be secreted by several cell types and regulates multiple processes, including cancer cell plasticity, angiogenesis and immune cell functions. However, the role of Gas6 in pancreatic cancer metastasis has not been fully investigated. In these studies we find that, in pancreatic tumors, Gas6 is mainly produced by tumor associated macrophages (TAMs) and cancer associated fibroblasts (CAFs) and that pharmacological blockade of Gas6 partially reverses epithelial-to-mesenchymal transition (EMT) of tumor cells and supports NK cell activation, thereby inhibiting pancreatic cancer metastasis. Our data suggest that Gas6 simultaneously acts on both the tumor cells and the NK cells to support pancreatic cancer metastasis. This study supports the rationale for targeting Gas6 in pancreatic cancer and use NK cells as a potential biomarker for response to anti-Gas6 therapy.</jats:p>

Item Type: Article
Uncontrolled Keywords: 32 Biomedical and Clinical Sciences, 3211 Oncology and Carcinogenesis, 3204 Immunology, Digestive Diseases, Rare Diseases, Cancer, Pancreatic Cancer, 2.1 Biological and endogenous factors, 2 Aetiology, Cancer
Depositing User: Symplectic Admin
Date Deposited: 02 Mar 2020 11:21
Last Modified: 21 Jun 2024 02:12
DOI: 10.1101/732149
Open Access URL: http://10.0.4.77/732149
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3076906