Reciprocal activation of cancer-associated fibroblasts and oral squamous carcinoma cells through CXCL1
Journal
Oral Oncology
Journal Volume
88
Pages
115-123
Date Issued
2019
Author(s)
Yeh C.-Y.
Yang C.-J.
Abstract
Objectives: Crosstalk between cancer cells and carcinoma-associated fibroblasts (CAFs) is known to be involved in various aspects of tumor biology, including during invasion. Using oral squamous cell carcinoma (OSCC) cells as a model, we examined whether and how CAFs respond to inflammatory signals to influence cancer cell migration and invasion. Materials and methods: Chemokine signatures within the human HNSCC datasets from The Cancer Genome Atlas (TCGA) were analyzed together with tissue assessment using immunohistochemical staining (IHC) and real-time PCR. A co-culture system was used to identify reciprocal effects exerted by CAFs and cancer cells upon one another. Recombinant CXCL1, CXCL1 neutralizing antibodies, and CXCR2 antagonist were used to confirm CXCL1/CXCR2 axis-mediated cell behaviors. Results: Analysis of the TCGA dataset revealed that CXCL1 is associated with poor survival, and IHC demonstrated CXCL1 is highly expressed in OSCC stromal cells. Moreover, real-time PCR showed that in addition to CXCL1, IL-1β and CXCR2 are also highly expressed in OSCC and IL-1β mRNA levels positively correlate with CXCL1 expression. Furthermore, CAFs co-cultured with SAS, a poorly differentiated OSCC cell line, or stimulated with IL-1β exhibit increased CXCL1 secretion in an NF-κB-dependent manner. Treatment of SAS cells with CAF-conditioned medium or CXCL1 increased their invasion and migration capabilities, indicating a reciprocal activation between CAFs and cancer cells. Moreover, CXCL-1 upregulated matrix metalloprotease-1 (MMP-1) expression and activity in CAFs. Conclusion: The induction of IL-1β following CXCL1 stimulation of CAFs mediates cancer cell invasion, and there is a reciprocal dependency between CAFs and cancer cells in the OSCC microenvironment. ? 2018 Elsevier Ltd
Other Subjects
1 (2 bromophenyl) 3 (2 hydroxy 4 nitrophenyl)urea; chemokine receptor CXCR2; CXCL1 chemokine; immunoglobulin enhancer binding protein; interleukin 1beta; interleukin 8; interstitial collagenase; messenger RNA; neutralizing antibody; carbanilamide derivative; chemokine receptor CXCR2; CXCL1 chemokine; CXCL1 protein, human; CXCR2 protein, human; IL1B protein, human; interleukin 1beta; interstitial collagenase; MMP1 protein, human; monoclonal antibody; Article; cancer associated fibroblast; cancer cell culture; cancer survival; carcinogenesis; cell activation; cell differentiation; cell invasion; cell migration; cell survival; clinical article; coculture; controlled study; cytokine release; enzyme activity; human; human cell; human tissue; immunohistochemistry; molecular pathology; mouth squamous cell carcinoma; mRNA expression level; paracrine signaling; priority journal; protein expression level; real time polymerase chain reaction; SAS cell line; survival rate; tumor microenvironment; upregulation; cancer associated fibroblast; cell motion; conditioned medium; drug effect; genetics; immunology; metabolism; mouth tumor; paracrine signaling; pathology; squamous cell carcinoma; tumor cell line; tumor invasion; Antibodies, Monoclonal; Cancer-Associated Fibroblasts; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Chemokine CXCL1; Coculture Techniques; Culture Media, Conditioned; Humans; Interleukin-1beta; Matrix Metalloproteinase 1; Mouth Neoplasms; Neoplasm Invasiveness; Paracrine Communication; Phenylurea Compounds; Progression-Free Survival; Receptors, Interleukin-8B; Tumor Microenvironment
Type
journal article