In vivo invasion of head and neck squamous cell carcinoma cells does not require macrophages.
In vivo invasion of head and neck squamous cell carcinoma cells does not require macrophages.
复制标题
头颈鳞状细胞癌细胞在体内的侵袭不需要巨噬细胞。
DOI：
10.1016/j.ajpath.2011.02.030
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Segall,JeffreyE
中科院分区：
文献类型：
--
作者：
Smirnova,Tatiana;Adomako,Alfred;Locker,Joseph;VanRooijen,Nico;Prystowsky,MichaelB;Segall,JeffreyE
肿瘤细胞侵入局部间质是癌症进展的重要组成部分。在这里，我们报告的thein在体内的头颈部鳞状细胞癌（HNSCC）细胞的侵袭响应于应用梯度的生长因子[表皮生长因子（EGF）]和趋化因子（CXCL 12），使用原位口底模型。对侵入细胞的分析表明，其中>75%为肿瘤细胞，约15%为巨噬细胞，<10%为未鉴定细胞。令人惊讶的是，虽然巨噬细胞与肿瘤细胞一起侵入，但巨噬细胞的贡献不是HNSCC侵入所必需的。还观察到CXCL 12诱导的HNSCC细胞的体内侵袭，并发现其通过表皮生长因子受体（EGFR）通过CXCR 4的单向反式激活而发生。使用TNF-α蛋白酶抑制剂-2抑制肿瘤坏死因子-α转换酶选择性抑制CXCL 12诱导的侵袭，但不抑制EGF诱导的侵袭，这与CXCL 12通过释放EGFR配体激活EGFR一致。
Invasion of tumor cells into the local stroma is an important component in cancer progression. Here we report studies of thein vivoinvasion of head and neck squamous cell carcinoma (HNSCC) cells in response to applied gradients of a growth factor [epidermal growth factor (EGF)] and a chemokine (CXCL12), using orthotopic floor-of-mouth models. Analysis of the invading cells indicated that >75% of them were tumor cells, about 15% macrophages, and <10% were unidentified. Surprisingly, although macrophages invaded together with tumor cells, macrophage contributions were not required for HNSCC invasion. CXCL12-inducedin vivoinvasion of HNSCC cells was also observed and found to occur via a unidirectional transactivation of epidermal growth factor receptor (EGFR) through CXCR4. Inhibition of tumor necrosis factor-α–converting enzyme using TNF-α protease inhibitor-2 selectively inhibited CXCL12-induced invasion but not EGF-induced invasion, consistent with CXCL12 activation of EGFR via release of EGFR ligands.