Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma
Stromal cells in the tumor microenvironment promote the progression of oral squamous cell carcinoma
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DOI：
10.3892/ijo.2021.5252
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发表时间：
2021-09-01
影响因子：
5.2
通讯作者：
Nagatsuka, Hitoshi
中科院分区：
文献类型：
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作者：
Shan, Qiusheng;Takabatake, Kiyofumi;Nagatsuka, Hitoshi
肿瘤微环境（TME）中的基质细胞可以影响多种类型癌症的进展;然而，关于口腔鳞状细胞癌（OSCC）的数据有限。本研究采用Giemsa染色、MTS和Transwell（invasion and migration）法分别观察疣状鳞状细胞癌相关基质细胞（VSCC-SCs）、鳞状细胞癌相关基质细胞（SCC-SCs）和人皮肤成纤维细胞（HDFs）对HSC-3细胞体外肿瘤巢形成、增殖、侵袭和迁移的影响。结果表明，VSCC-SCs和SCC-SCs在体外均能抑制肿瘤巢的形成，促进OSCC细胞的增殖、侵袭和迁移。分别采用苏木精-伊红染色、抗酒石酸酸性磷酸酶染色、免疫组化和双荧光免疫组化染色，观察VSCC-SCs、SCC-SCs和HDFs对口腔鳞癌细胞分化、增殖、侵袭和迁移的影响。结果表明，VSCC-SCs促进OSCC细胞的分化、增殖、侵袭和迁移，而SCC-SCs抑制OSCC细胞的分化，促进OSCC细胞的增殖、侵袭和迁移。最后，使用微阵列数据预测VSCC-SCs和SCC-SCs中可能影响OSCC进展的基因，以及那些有可能影响VSCC-SCs和SCC-SCs对OSCC分化的差异效应的基因。研究发现，C-X-C基序趋化因子配体（CXCL）8、丝裂原活化蛋白激酶3（MAPK 3）、磷脂酰肌醇-4，5-二磷酸3-激酶催化亚基α（PIK 3CA）、C-X-C基序趋化因子配体1（CXCL 1）和C-C基序趋化因子配体2（CCL 2）可能参与VSCC-SCs、SCC-SCs和OSCC细胞之间的串扰，从而调节OSCC的进展。细胞间粘附分子1（ICAM 1）、白细胞介素1B（IL 1B）、Fos原癌基因、AP-1转录因子亚基（FOS）、骨形态发生蛋白4（BMP 4）、胰岛素（INS）和神经生长因子（NGF）可能是VSCC-SCs和SCC-SCs在OSCC分化中发挥不同作用的机制。本研究结果表明，VSCC-SCs和SCC-SCs均能促进OSCC的发生发展，且SCC-SCs的促进作用更明显，这可能是OSCC发生发展的一种潜在调控机制。
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.