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Title: Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism

Abstract

CD147 is a multifunctional transmembrane protein and promotes cancer progression. We found that the anti-human CD147 mouse monoclonal antibody MEM-M6/1 strongly induces necrosis-like cell death in LoVo, HT-29, WiDr, and SW620 colon cancer cells and A2058 melanoma cells, but not in WI-38 and TIG-113 normal fibroblasts. Silencing or overexpression of CD147 in LoVo cells enhanced or decreased the MEM-M6/1 induced cell death, respectively. CD147 is known to form complex with proton-linked monocarboxylate transporters (MCTs), which is critical for lactate transport and intracellular pH (pHi) homeostasis. In LoVo cells, CD147 and MCT-1 co-localized on the cell surface, and MEM-M6/1 inhibited the association of these molecules. MEM-M6/1 inhibited lactate uptake, lactate release, and reduced pHi. Further, the induction of acidification was parallel to the decrease of the glycolytic flux and intracellular ATP levels. These effects were not found in the normal fibroblasts. As cancer cells depend on glycolysis for their energy production, CD147 inhibition might induce cell death specific to cancer cells.

Authors:
 [1];  [2];  [3];  [4]
  1. Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Research Institute, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511 (Japan), E-mail: baba-mi@mc.pref.osaka.jp
  2. Department of Tumor Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Research Institute, Higashinari-ku, Osaka (Japan)
  3. Department of Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Research Institute, Higashinari-ku, Osaka (Japan)
  4. Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Research Institute, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511 (Japan)
Publication Date:
OSTI Identifier:
21143858
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 374; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2008.06.122; PII: S0006-291X(08)01284-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACIDIFICATION; APOPTOSIS; ATP; ELECTROMECHANICS; FIBROBLASTS; GLYCOLYSIS; HOMEOSTASIS; LACTATES; LARGE INTESTINE; MELANOMAS; MICE; MICROSTRUCTURE; MONOCLONAL ANTIBODIES; NECROSIS; PH VALUE; PROTEINS

Citation Formats

Baba, Miyako, Inoue, Masahiro, Itoh, Kazuyuki, and Nishizawa, Yasuko. Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2008.06.122.
Baba, Miyako, Inoue, Masahiro, Itoh, Kazuyuki, & Nishizawa, Yasuko. Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism. United States. doi:10.1016/j.bbrc.2008.06.122.
Baba, Miyako, Inoue, Masahiro, Itoh, Kazuyuki, and Nishizawa, Yasuko. Fri . "Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism". United States. doi:10.1016/j.bbrc.2008.06.122.
@article{osti_21143858,
title = {Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism},
author = {Baba, Miyako and Inoue, Masahiro and Itoh, Kazuyuki and Nishizawa, Yasuko},
abstractNote = {CD147 is a multifunctional transmembrane protein and promotes cancer progression. We found that the anti-human CD147 mouse monoclonal antibody MEM-M6/1 strongly induces necrosis-like cell death in LoVo, HT-29, WiDr, and SW620 colon cancer cells and A2058 melanoma cells, but not in WI-38 and TIG-113 normal fibroblasts. Silencing or overexpression of CD147 in LoVo cells enhanced or decreased the MEM-M6/1 induced cell death, respectively. CD147 is known to form complex with proton-linked monocarboxylate transporters (MCTs), which is critical for lactate transport and intracellular pH (pHi) homeostasis. In LoVo cells, CD147 and MCT-1 co-localized on the cell surface, and MEM-M6/1 inhibited the association of these molecules. MEM-M6/1 inhibited lactate uptake, lactate release, and reduced pHi. Further, the induction of acidification was parallel to the decrease of the glycolytic flux and intracellular ATP levels. These effects were not found in the normal fibroblasts. As cancer cells depend on glycolysis for their energy production, CD147 inhibition might induce cell death specific to cancer cells.},
doi = {10.1016/j.bbrc.2008.06.122},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 374,
place = {United States},
year = {Fri Sep 12 00:00:00 EDT 2008},
month = {Fri Sep 12 00:00:00 EDT 2008}
}