Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes
Significance of cancer stroma for bone destruction in oral squamous cell carcinoma using different cancer stroma subtypes
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DOI：
10.3892/or.2022.8292
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发表时间：
2022-04-01
期刊：
影响因子：
4.2
通讯作者：
Nagatsuka, Hitoshi
中科院分区：
文献类型：
--
作者：
Shan, Qiusheng;Takabatake, Kiyofumi;Nagatsuka, Hitoshi
肿瘤微环境中的间质细胞(TME)可以调节多种癌症的进展，但口腔鳞状细胞癌(OSCC)的骨侵袭研究较少。本研究通过苏木精-伊红、AE1/3(泛细胞角蛋白)和抗酒石酸酸性磷酸酶染色，观察了疣状SCC相关基质细胞(VSCC-SCs)、SCC相关基质细胞(SCC-SCs)和人真皮成纤维细胞在体内对骨吸收和HSC-3破骨细胞活化的影响。采用免疫组织化学方法检测HSC-3细胞侵袭区基质金属蛋白酶9(MMP9)、膜型1 MMP1(MT1-MMPs)、核因子-kappaB受体激活剂配体(RANKL)和甲状旁腺激素相关肽(PTHrP)的表达水平。结果提示，SCC-SCs和VSCC-SCs均能促进骨吸收，促进破骨细胞活化，促进MMP9、MT1-MMPs、Snail、RANKL和PTHrP的表达。但与VSCC-SCs相比，SCC-SCs的作用更为显著。最后，利用微阵列数据预测口腔鳞癌中VSCC-SCs和SCC-SCs对骨侵袭的不同影响的潜在基因。结果表明，IL1B、ICAM1、FOS、CXCL12、INS和NGF可能是这种差异作用的基础。综上所述，VSCC-SCs和SCC-SCs均可通过上调PTHrP介导的RANKL在癌细胞和基质细胞中的表达来促进口腔鳞癌的骨侵袭，但SCC-SCs的作用更为显著。这些发现可能代表了口腔鳞癌骨侵袭的潜在调控机制。
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 metalloproteinase (MMP)9, membrane-type 1 MMP (MT1-MMP), Snail, receptor activator of NF-kappa B ligand (RANKL) and parathyroid hormone-related peptide (PTHrP) in the bone invasion regions of HSC-3 cells were examined by immunohistochemistry. 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.