TY - JOUR
T1 - Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes
AU - Shan, Qiusheng
AU - Takabatake, Kiyofumi
AU - Kawai, Hotaka
AU - Oo, May Wathone
AU - Inada, Yasunori
AU - Sukegawa, Shintaro
AU - Fushimi, Shigeko
AU - Nakano, Keisuke
AU - Nagatsuka, Hitoshi
N1 - Funding Information:
This work was supported by the Japan Society for Promotion of Science (JSPS) KAKENHI Grants‑in‑Aid for Scientific Research (grant nos. JP21K17089, JP19K19159, JP20K10178, JP20H03888 and JP21K10043).
Publisher Copyright:
© 2022 Spandidos Publications. All rights reserved.
PY - 2022/4
Y1 - 2022/4
N2 - Stromal cells in the tumor microenvironment (TME) can regulate the progression of numerous types of cancer; however, the bone invasion of oral squamous cell carcinoma (OSCC) has been poorly investigated. In the present study, the effect of verrucous SCC-associated stromal cells (VSCC-SCs), SCC-associated stromal cells (SCC-SCs) and human dermal fibroblasts on bone resorption and the activation of HSC-3 osteoclasts in vivo were examined by hematoxylin and eosin, AE1/3 (pan-cytokeratin) and tartrate-resistant acid phosphatase staining. In addition, the expression levels of matrix metal- loproteinase (MMP)9, membrane-type 1 MMP (MT1-MMP), Snail, receptor activator of NF-κB ligand (RANKL) and para- thyroid hormone-related peptide (PTHrP) in the bone invasion regions of HSC-3 cells were examined by immunohistochem- istry. The results suggested that both SCC-SCs and VSCC-SCs promoted bone resorption, the activation of osteoclasts, and the expression levels of MMP9, MT1-MMP, Snail, RANKL and PTHrP. However, SCC-SCs had a more prominent effect compared with VSCC-SCs. Finally, microarray data were used to predict potential genes underlying the differential effects of VSCC-SCs and SCC-SCs on bone invasion in OSCC. The results revealed that IL1B, ICAM1, FOS, CXCL12, INS and NGF may underlie these differential effects. In conclusion, both VSCC-SCs and SCC-SCs may promote bone invasion in OSCC by enhancing the expression levels of RANKL in cancer and stromal cells mediated by PTHrP; however, SCC-SCs had a more prominent effect. These findings may represent a potential regulatory mechanism underlying the bone invasion of OSCC.
AB - Stromal cells in the tumor microenvironment (TME) can regulate the progression of numerous types of cancer; however, the bone invasion of oral squamous cell carcinoma (OSCC) has been poorly investigated. In the present study, the effect of verrucous SCC-associated stromal cells (VSCC-SCs), SCC-associated stromal cells (SCC-SCs) and human dermal fibroblasts on bone resorption and the activation of HSC-3 osteoclasts in vivo were examined by hematoxylin and eosin, AE1/3 (pan-cytokeratin) and tartrate-resistant acid phosphatase staining. In addition, the expression levels of matrix metal- loproteinase (MMP)9, membrane-type 1 MMP (MT1-MMP), Snail, receptor activator of NF-κB ligand (RANKL) and para- thyroid hormone-related peptide (PTHrP) in the bone invasion regions of HSC-3 cells were examined by immunohistochem- istry. The results suggested that both SCC-SCs and VSCC-SCs promoted bone resorption, the activation of osteoclasts, and the expression levels of MMP9, MT1-MMP, Snail, RANKL and PTHrP. However, SCC-SCs had a more prominent effect compared with VSCC-SCs. Finally, microarray data were used to predict potential genes underlying the differential effects of VSCC-SCs and SCC-SCs on bone invasion in OSCC. The results revealed that IL1B, ICAM1, FOS, CXCL12, INS and NGF may underlie these differential effects. In conclusion, both VSCC-SCs and SCC-SCs may promote bone invasion in OSCC by enhancing the expression levels of RANKL in cancer and stromal cells mediated by PTHrP; however, SCC-SCs had a more prominent effect. These findings may represent a potential regulatory mechanism underlying the bone invasion of OSCC.
KW - bone invasion
KW - cancer-associated stromal cells
KW - microarray
KW - Oral squamous cell carcinoma
KW - osteoclast
KW - parathyroid hormone-related peptide
KW - receptor activator of NF-κB ligand
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U2 - 10.3892/or.2022.8292
DO - 10.3892/or.2022.8292
M3 - Article
C2 - 35211756
AN - SCOPUS:85125336342
VL - 47
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 4
M1 - 81
ER -