NDLI: Cancer-Associated Fibroblasts Promote Tumor Aggressiveness in Head and Neck Cancer through Chemokine Ligand 11 and C-C Motif Chemokine Receptor 3 Signaling Circuit

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Cancer-Associated Fibroblasts Promote Tumor Aggressiveness in Head and Neck Cancer through Chemokine Ligand 11 and C-C Motif Chemokine Receptor 3 Signaling Circuit

Content Provider	MDPI
Author	Huang, Wen-Yen Lin, Yaoh-Shiang Lin, Yu-Chun Nieh, Shin Chang, Yi-Ming Lee, Tsai-Yu Chen, Su-Feng Yang, Kuender D.
Copyright Year	2022
Description	The tumor microenvironment (TME) plays a crucial role in tumor progression. One of its key stromal components, cancer-associated fibroblasts (CAFs), may crosstalk with cancer cells by secreting certain cytokines or chemokines. However, which important mediator(s) are released by CAFs, and the underlying molecular mechanism, remain largely unknown. In the present study, we isolated patient-derived CAFs and normal fibroblasts (NFs). Using microarray analysis, we detected chemokine ligand 11 (CCL11) overexpression in CAFs compared to NFs. CCL11 administration promoted the migration and invasion of head and neck cancer (HNC) cells with enhanced cancer stem cell-like properties and induction of epithelial-to-mesenchymal transition. Furthermore, neutralization of CCL11 activity reversed the aggressive phenotype of CAF-induced cancer cells. Confocal microscopy showed colocalization of CCL11 and CC chemokine receptor 3 (CCR3) on HNC cells. Moreover, immunohistochemical analysis of clinical samples from 104 patients with HNC showed that expression of CCL11 and CCR3 were significantly correlated with poor overall survival (p = 0.003 and 0.044, respectively). Collectively, CCL11 expressed on CAFs promotes HNC invasiveness, and neutralization of CCL11 reverses this effect. We propose that the CCL11/CCR3 signaling circuit is a potential target for optimizing therapeutic strategies against HNC.
Starting Page	3141
e-ISSN	20726694
DOI	10.3390/cancers14133141
Journal	Cancers
Issue Number	13
Volume Number	14
Language	English
Publisher	MDPI
Publisher Date	2022-06-27
Access Restriction	Open
Subject Keyword	Cancers Oncology Head and Neck Cancer Cancer-associated Fibroblasts Ccl11 Ccr3 Tumor Microenvironment
Content Type	Text
Resource Type	Article

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