Enhanced glucose metabolism mediated by CD147 is associated with 18 F-FDG PET/CT imaging in lung adenocarcinoma

Thorac Cancer. 2020 May;11(5):1245-1257. doi: 10.1111/1759-7714.13383. Epub 2020 Mar 11.

Abstract

Background: Lung adenocarcinoma (LUAD) is one of the most deadly thoracic tumors. Reprogrammed glycolytic metabolism is a hallmark of cancer cells and significantly affects several cellular functions. In the current study, we aimed to investigate cluster of differentiation 147 (CD147)-mediated glucose metabolic regulation in LUAD and its association with 18 F-FDG PET/CT imaging.

Methods: The expression profile and prognostic potential of CD147 in LUAD were analyzed using UALCAN and a Kaplan-Meier plotter. Tissue immunohistochemical analyses and PET metabolic parameters were used to identify the relationship between CD147 expression and reprogrammed glycolysis. The role of CD147 in glucose metabolic reprogramming was assessed by radioactive uptake of 18 F-FDG through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo. Western blotting assays were used to determine the expression level of monocarboxylate transporter 1 (MCT1) and MCT4 in established human LUAD cell lines (ie, HCC827 and H1975) with different CD147 expression levels via lentiviral transduction.

Results: CD147 was highly expressed in LUAD. A significant positive correlation existed between CD147 expression and PET metabolic parameters(SUVmax,SUVmean, SUVpeak). CD147 could promote radioactive uptake of 18 F-FDG in vitro and in vivo, suggesting the ability of CD147 to enhance glycolytic metabolism. Furthermore, as an obligate chaperone for MCT1 and MCT4, CD147 positively correlated with MCT1 and MCT4 expression in LUAD tissues and established cell lines with different CD147 expression.

Conclusions: Our study revealed that CD147 is a promising novel target for LUAD treatment and CD147-mediated glucose metabolism demonstrated its contribution to the predictive role of 18 F-FDG PET/CT imaging for targeted therapeutic efficacy.

Keywords: 18F-FDG PET/CT imaging; CD147; glucose metabolism; lung adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / diagnostic imaging
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology*
  • Adenocarcinoma of Lung / surgery
  • Animals
  • Apoptosis
  • Basigin / metabolism*
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Female
  • Fluorodeoxyglucose F18*
  • Glucose / metabolism*
  • Glycolysis
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Positron Emission Tomography Computed Tomography / methods*
  • Prognosis
  • Radiopharmaceuticals*
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • BSG protein, human
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Basigin
  • Glucose