Cancer‑associated fibroblast stimulates cancer cell invasion in an interleukin‑1 receptor (IL‑1R)‑dependent manner

Zhang,Xianglan; Hwang,Young  Sun

doi:10.3892/ol.2019.10784

Cancer‑associated fibroblast stimulates cancer cell invasion in an interleukin‑1 receptor (IL‑1R)‑dependent manner

Authors:
- Xianglan Zhang
- Young Sun Hwang
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Affiliations: Department of Pathology, Yanbian University Hospital, Yanji, Jilin 133000, P.R. China, Department of Dental Hygiene, College of Health Science, Eulji University, Seongnam, Gyunggi‑Do 13135, Republic of Korea
Published online on: August 27, 2019 https://doi.org/10.3892/ol.2019.10784
Pages: 4645-4650
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumor microenvironment serves an important role in tumor growth and metastasis. Cancer cells can promote growth and malignancy by altering the surrounding stroma. Cancer‑associated fibroblast (CAF) are an abundant cell type present within the tumor microenvironment and provide tumorigenic features by secreting cytokines. In the current study, the CAF‑mediated invasion of oral squamous cell carcinoma (OSCC) was investigated and the associated mechanisms were elucidated. Cancer invasion was estimated using a Matrigel‑coated Transwell chamber and FITC‑gelatin matrix. To verify the effect of the tumor microenvironment, conditioned media (CM) from normal fibroblast (NF) and CAFs were prepared. An ELISA was performed to estimate the level of IL‑1β. A proteome profiler human protease array was performed to verify the proteases affected by stimulation with CM, from CAF. Recombinant IL‑1β protein increased the invasion of OSCC cells. IL‑1β expression was higher in CAF than NF. CM from CAF (CM‑CAF) increased cancer invasion and FITC‑gelatin matrix degradation. The invasive capacity provided by CAF was abrogated by an IL‑1 receptor (IL‑1R) antagonist. Additionally, CM‑CAF increased the secretion of ADAM 9 and Kallikrein 11 from OSCC cells. The invasion activity by CM‑CAF was partially abrogated by the neutralization of ADAM 9 or Kallikrein 11. In conclusion, by providing stromal factor, CAFs were a critical inducer of OSCC invasion, and CAF secretes the required amount of IL‑1β to increase cancer invasion activity. The invasive capacity of CAF was identified to be IL‑1R‑dependent. ADAM 9 and Kallikrein 11 were influencing factors involved in the increase of CAF‑mediated cancer invasion.

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