Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line‑derived xenograft model

Shan,Qiusheng; Takabatake,Kiyofumi; Omori,Haruka; Kawai,Hotaka; Oo,May Wathone; Sukegawa,Shintaro; Fujii,Masae; Inada,Yasunori; Sano,Sho; Nakano,Keisuke; Nagatsuka,Hitoshi

doi:10.3892/ol.2022.13502

Investigation of bone invasion and underlying mechanisms of oral cancer using a cell line‑derived xenograft model

Authors:
- Qiusheng Shan
- Kiyofumi Takabatake
- Haruka Omori
- Hotaka Kawai
- May Wathone Oo
- Shintaro Sukegawa
- Masae Fujii
- Yasunori Inada
- Sho Sano
- Keisuke Nakano
- Hitoshi Nagatsuka
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Affiliations: Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama 700‑8525, Japan
Published online on: September 13, 2022 https://doi.org/10.3892/ol.2022.13502
Article Number: 382
Copyright: © Shan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The cancer stroma regulates bone invasion in oral squamous cell carcinoma (OSCC). However, data on normal stroma are limited. In the present study, the effects of gingival and periodontal ligament tissue‑derived stromal cells (G‑SCs and P‑SCs, respectively) and human dermal fibroblasts (HDFs) on bone resorption and osteoclast activation were assessed using hematoxylin and eosin and tartrate‑resistant acid phosphatase staining in a cell line‑derived xenograft model. The results demonstrated that G‑SCs promoted bone invasion and osteoclast activation and inhibited osteoclast proliferation following crosstalk with the human OSCC HSC‑3 cell line, whereas P‑SCs inhibited bone resorption and promoted osteoclast proliferation in vitro but had a minimal effect on osteoclast activation both in vitro and in vivo following crosstalk with HSC‑3 cells. Furthermore, the effects of G‑SCs, P‑SCs and HDFs on protein expression levels of matrix metalloproteinase (MMP)‑9, membrane type 1 MMP (MT1‑MMP), Snail, parathyroid hormone‑related peptide (PTHrP) and receptor activator of NF‑κB ligand (RANKL) in HSC‑3 cells in OSCC bone invasion regions were assessed using immunohistochemistry. The results demonstrated that G‑SCs had a more prominent effect on the expression of MMP‑9, MT1‑MMP, Snail, PTHrP, and RANKL, whereas P‑SCs only promoted RANKL and PTHrP expression and exerted a minimal effect on MMP‑9, MT1‑MMP and Snail expression. The potential genes underlying the differential effects of G‑SCs and P‑SCs on bone invasion in OSCC were evaluated using a microarray, which indicated that cyclin‑dependent kinase 1, insulin, aurora kinase A, cyclin B1 and DNA topoisomerase II alpha underlaid these differential effects. Therefore, these results demonstrated that G‑SCs promoted bone invasion in OSCC by activating osteoclasts on the bone surface, whereas P‑SCs exerted an inhibitory effect. These findings could indicate a potential regulatory mechanism for bone invasion in OSCC.

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