Sp1 induced gene TIMP1 is related to immune cell infiltration in glioblastoma

Sci Rep. 2022 Jul 1;12(1):11181. doi: 10.1038/s41598-022-14751-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis
  • Cell Line, Tumor
  • Glioblastoma* / immunology
  • Glioblastoma* / pathology
  • Humans
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Sp1 Transcription Factor* / genetics
  • Sp1 Transcription Factor* / immunology
  • Tissue Inhibitor of Metalloproteinase-1* / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-1* / genetics
  • Tissue Inhibitor of Metalloproteinase-1* / immunology
  • Tumor Microenvironment / immunology

Substances

  • Sp1 Transcription Factor
  • SP1 protein, human
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1