TLR family gene expression in relation to the HIF1α and the VEGFR pathway activation in endometrial cancer

Ginekol Pol. 2020;91(8):439-446. doi: 10.5603/GP.2020.0073.

Abstract

Introduction: Malignant neoplasm of the endometrium is the most common malignant neoplasm of the female reproductive system. Toll Like Receptors (TLR) play a significant role in innate and late-immunity against infections or damaged tissues. TLRs are also involved in the development of tumors in their natural microenvironment. TLRs play an important role in angiogenesis, necessary for survival and growth of the tumor. Hypoxia playing a critical role in angiogenesis, carcinogenesis, tumor progression and distant metastasis is primarily mediated through hypoxia inducible factors (HIFs). Vascular endothelial growth factor family proteins (VEGF) are also strongly involved in tumor angiogenesis and their action is strongly associated with TLR receptors.

Objectives: The aim of the study was to correlate the expression of selected TLRs and VEGFR's as well as HIF1α with clinicopathological data of endometrial cancer patients.

Material and methods: 123 neoplastic endometrial samples were included in the study. 51 samples of healthy endometrium served as control. The expression of TLR1, TLR2, TLR3, TLR4, VEGFR1 and VEGFR2, VEGF-A and HIF1α was examined after RNA isolation at the mRNA level by Real Time-PCR.

Results: We have noted a significant correlation between the expression of selected TLR and VEGFR's and clinical stage as well as pathological grading of endometrial cancer.

Conclusions: Received correlations confirm a significant contribution of some TLR expression and the receptor for VEGF in the pathogenesis of epithelial endometrial cancer.

Keywords: HIF1-α; TLR family; VEGF; VEGFR1; VEGR2; endometrial cancer.

MeSH terms

  • Adult
  • Case-Control Studies
  • Endometrial Neoplasms / metabolism*
  • Endometrium / metabolism*
  • Female
  • Gene Expression
  • Humans
  • Receptors, Vascular Endothelial Growth Factor / metabolism*
  • Signal Transduction / physiology
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*

Substances

  • FLT1 protein, human
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1