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Crosstalk between head and neck cancer cells and lymphatic endothelial cells promotes tumor metastasis via CXCL5‐CXCR2 signaling
Author(s) -
Lee BokSoon,
Jang Jeon Yeob,
Seo Chorong,
Kim ChulHo
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001455r
Subject(s) - head and neck squamous cell carcinoma , cancer research , metastasis , lymphatic system , cancer cell , medicine , crosstalk , tumor microenvironment , chemokine , lymphatic endothelium , cxcl5 , cancer , head and neck cancer , pathology , receptor , tumor cells , physics , optics
Abstract Head and neck squamous cell carcinoma (HNSCC) metastasizes to the locoregional lymph nodes at high rates and is related to poor clinical outcomes. However, the mechanism by which cancer cells migrate to the lymph nodes is unclear. To address this, we established a conditioned medium culture system for HNSCC cells and lymphatic endothelial cells (LECs) and investigated their crosstalk. Stimulation with tumor‐conditioned medium (TCM) activated LECs, resulting in a robust increase in cell proliferation to induce lymphatic hyperplasia. Further, stimulation of HNSCC cells with activated LEC Conditioned media (TCM‐LEC CM) induced cell invasion. Among various chemokines, CXCL5 promoted the invasion of TCM‐LEC CM‐treated HNSCC cells. The level of CXCL5 protein was higher in cancer tissues than those in normal tissues from HNSCC patients. Furthermore, treatment with SB225002, a CXCR2 (CXCL5 receptor) inhibitor, resulted in decreased lymph node metastasis in vivo. In conclusion, inhibition of CXCL5‐CXCR2 signaling between cancer cells and LECs suppresses cancer cell invasion and metastasis in vitro and in vivo. This novel therapeutic strategy might be a practical approach to the clinical management of HNSCC.