Li Xin
Allergy department, The First Affiliated Hospital of Liaoning Medical University, No. 2, Section 5, Renmin Road, Jinzhou, 121001, China.
Tumour Biol. 2016 Apr;37(4):5585-90. doi: 10.1007/s13277-015-4388-9. Epub 2015 Nov 15.
Tumor-associated macrophages (TAMs) play an essential role in the immunology, growth, invasion, and metastases of skin squamous cell carcinoma (SCC). However, the molecular mechanisms underlying the activation and regulation of TAMs by SCC are not completely understood. Here, in a Transwell co-culture system, we found that SCC cells induced polarization of macrophages to a M2 phenotype, evident by expression of surface markers CD163, CD206, and CD301, as well as reduction of cellular iNOS levels and augmentation of cellular arginase levels. Moreover, tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) was induced in macrophages by co-culturing with SCC cells. Depletion of TIPE2 in macrophages abolished the effects of co-cultured SCC cells on phenotypic modification of macrophages. Furthermore, patients with SCC were divided into two groups based on TIPE2 levels in TAMs at the time of tumor resection. We found that patients with high-TIPE2 TAMs had an overall poor 5-year survival. Together, our data suggest a previously unappreciated role of TIPE2 in the crosstalk between skin SCC and TAMs and highlight TIPE2 as a promising novel target for skin SCC treatment.
肿瘤相关巨噬细胞（TAM）在皮肤鳞状细胞癌（SCC）的免疫、生长、侵袭和转移中起着至关重要的作用。然而，SCC激活和调节TAM的分子机制尚未完全阐明。在此，在Transwell共培养系统中，我们发现SCC细胞诱导巨噬细胞极化为M2表型，表现为表面标志物CD163、CD206和CD301的表达，以及细胞诱导型一氧化氮合酶（iNOS）水平的降低和细胞精氨酸酶水平的升高。此外，通过与SCC细胞共培养，巨噬细胞中诱导肿瘤坏死因子（TNF）-α诱导蛋白8样2（TIPE2）。巨噬细胞中TIPE2的缺失消除了共培养的SCC细胞对巨噬细胞表型修饰的影响。此外，根据肿瘤切除时TAM中TIPE2水平将SCC患者分为两组。我们发现，TIPE2水平高的TAM患者的5年总生存率较差。总之，我们的数据表明TIPE2在皮肤SCC与TAM的相互作用中具有先前未被认识的作用，并突出了TIPE2作为皮肤SCC治疗的一个有前景的新靶点。
