Expression of Insulin-Like Growth Factor Type 1 Receptor Is Linked to Inflammation in Adamantinomatous Craniopharyngioma

Neuroendocrinology. 2022;112(9):917-926. doi: 10.1159/000521458. Epub 2021 Dec 13.

Abstract

Introduction: Insulin-like growth factor type 1 receptor (IGF1R) is overexpressed in various malignant tumors, which relates to their transformation and recurrence. Craniopharyngioma is a benign tumor with malignant results, often accompanied by a severe inflammatory reaction. However, the relationship between IGF1R expression and the inflammatory response of craniopharyngioma is unclear.

Methods: We enrolled 85 patients with adamantinomatous craniopharyngioma (ACP) in a study to explore the relationship between IGF1R expression and clinical features of this disease.

Results: Patients in the IGF1R high-expression group had a significantly higher incidence of hypopituitarism, higher recurrence rate, and lower progression-free survival. β-Catenin can further regulate expression of the stem cell marker, CD44, by regulating IGF1R. Using immunofluorescence, we found that tumor stem cell-like cells did not express phosphorylated (p)-ERK, although p-ERK activation was evident in the surrounding cells. Picropodophyllin, a specific inhibitor of IGF1R, increased the expression of p-ERK protein and decreased the transcription level of interleukin-6.

Conclusions: High expression of IGF1R might promote inflammation of ACP, which might be an unfavorable factor for pituitary function and prognosis. The high expression of IGF1R in tumor stem cell-like cells might inhibit the expression of p-ERK and promote the generation of inflammatory factors. IGF1R plays a stemness maintenance role in ACP and regulates the production of inflammatory factors through a p-ERK pathway, which suggests that targeting IGF1R and p-ERK might provide a new direction for alleviating tumor inflammation.

Keywords: Adamantinomatous craniopharyngioma; Inflammation; Insulin-like growth factor type 1 receptor; Tumor stem cell-like cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Craniopharyngioma* / pathology
  • Humans
  • Inflammation / metabolism
  • Pituitary Gland / metabolism
  • Pituitary Neoplasms* / pathology
  • Receptor, IGF Type 1* / metabolism

Substances

  • IGF1R protein, human
  • Receptor, IGF Type 1