Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, People's Republic of China.
Department of Neurosurgery, Guangzhou Women and Children's Medical Center, Guangzhou, 510623, Guangdong, People's Republic of China.
Sci Rep. 2022 Jul 1;12(1):11181. doi: 10.1038/s41598-022-14751-4.
Tumor immune microenvironment exerts a profound effect on the population of infiltrating immune cells. Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is frequently overexpressed in a variety of cells, particularly during inflammation and tissue injury. However, its function in cancer and immunity remains enigmatic. In this study, we find that TIMP1 is substantially up-regulated during tumorigenesis through analyzing cancer bioinformatics databases, which is further confirmed by IHC tissue microarrays of clinical samples. The TIMP1 level is significantly increased in lymphocytes infiltrating the tumors and correlated with cancer progression, particularly in GBM. Notably, we find that the transcriptional factor Sp1 binds to the promoter of TIMP1 and triggers its expression in GBM. Together, our findings suggest that the Sp1-TIMP1 axis can be a potent biomarker for evaluating immune cell infiltration at the tumor sites and therefore, the malignant progression of GBM.
肿瘤免疫微环境对浸润免疫细胞的群体有深远影响。组织金属蛋白酶抑制剂 1（TIMP1）在多种细胞中经常过表达，特别是在炎症和组织损伤期间。然而，其在癌症和免疫中的功能仍然是个谜。在这项研究中，我们通过分析癌症生物信息学数据库发现 TIMP1 在肿瘤发生过程中大量上调，这进一步通过临床样本的 IHC 组织微阵列得到证实。TIMP1 水平在浸润肿瘤的淋巴细胞中显著增加，并与癌症进展相关，尤其是在 GBM 中。值得注意的是，我们发现转录因子 Sp1 结合到 TIMP1 的启动子上，并在 GBM 中触发其表达。总之，我们的研究结果表明，Sp1-TIMP1 轴可以作为评估肿瘤部位免疫细胞浸润的有力生物标志物，因此也是 GBM 恶性进展的标志物。
