Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma.

Content Provider	Europe PMC
Author	Shan, Qiusheng Takabatake, Kiyofumi Omori, Haruka Kawai, Hotaka Oo, May Wathone Nakano, Keisuke Ibaragi, Soichiro Sasaki, Akira Nagatsuka, Hitoshi
Copyright Year	2021
Abstract	The stromal cells in the tumor microenvironment (TME) can influence the progression of multiple types of cancer; however, data on oral squamous cell carcinoma (OSCC) are limited. In the present study, the effects of verrucous squamous cell carcinoma-associated stromal cells (VSCC-SCs), squamous cell carcinoma-associated stromal cells (SCC-SCs) and human dermal fibroblasts (HDFs) on the tumor nest formation, proliferation, invasion and migration of HSC-3 cells were examined in vitro using Giemsa staining, MTS, and Transwell (invasion and migration) assays, respectively. The results revealed that both the VSCC-SCs and SCC-SCs inhibited the tumor nest formation, and promoted the proliferation, invasion and migration of OSCC cells in vitro. Furthermore, the effects of VSCC-SCs, SCC-SCs and HDFs on the differentiation, proliferation, invasion and migration of OSCC cells in vivo were evaluated by hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, immunohistochemistry and double-fluorescent immunohistochemical staining, respectively. The results demonstrated that the VSCC-SCs promoted the differentiation, proliferation, invasion and migration of OSCC cells, while the SCC-SCs inhibited the differentiation, and promoted the proliferation, invasion and migration of OSCC cells in vivo. Finally, microarray data were used to predict genes in VSCC-SCs and SCC-SCs that may influence the progression of OSCC, and those with potential to influence the differential effects of VSCC-SCs and SCC-SCs on the differentiation of OSCC. It was found that C-X-C motif chemokine ligand (CXCL)8, mitogen-activated protein kinase 3 (MAPK3), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), C-X-C motif chemokine ligand 1 (CXCL1) and C-C motif chemokine ligand 2 (CCL2) may be involved in the crosstalk between VSCC-SCs, SCC-SCs and OSCC cells, which regulates the progression of OSCC. Intercellular adhesion molecule 1 (ICAM1), interleukin (IL)1B, Fos proto-oncogene, AP-1 transcription factor subunit (FOS), bone morphogenetic protein 4 (BMP4), insulin (INS) and nerve growth factor (NGF) may be responsible for the differential effects of VSCC-SCs and SCC-SCs on the differentiation of OSCC. On the whole, the present study demonstrates that both VSCC-SCs and SCC-SCs may promote the progression of OSCC, and SCC-SCs were found to exert a more prominent promoting effect; this may represent a potential regulatory mechanism for the progression of OSCC.
ISSN	10196439
Journal	International Journal of Oncology
Volume Number	59
PubMed Central reference number	PMC8360621
Issue Number	3
PubMed reference number	34368860
e-ISSN	17912423
DOI	10.3892/ijo.2021.5252
Language	English
Publisher	D.A. Spandidos
Publisher Date	2021-08-09
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Shan et al.
Subject Keyword	oral squamous cell carcinoma stromal cells differentiation proliferation invasion migration microarray
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology