An IgM monoclonal antibody against domain 1 of CD147 induces non-canonical RIPK-independent necroptosis in a cell type specific manner in hepatocellular carcinoma cells
Issued Date
2022-09-01
Resource Type
ISSN
01674889
eISSN
18792596
Scopus ID
2-s2.0-85130539731
Pubmed ID
35598753
Journal Title
Biochimica et Biophysica Acta - Molecular Cell Research
Volume
1869
Issue
9
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biochimica et Biophysica Acta - Molecular Cell Research Vol.1869 No.9 (2022)
Suggested Citation
Pomlok K., Pata S., Kulaphisit M., Pangnuchar R., Wipasa J., Smith D.R., Kasinrerk W., Lithanatudom P. An IgM monoclonal antibody against domain 1 of CD147 induces non-canonical RIPK-independent necroptosis in a cell type specific manner in hepatocellular carcinoma cells. Biochimica et Biophysica Acta - Molecular Cell Research Vol.1869 No.9 (2022). doi:10.1016/j.bbamcr.2022.119295 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/87118
Title
An IgM monoclonal antibody against domain 1 of CD147 induces non-canonical RIPK-independent necroptosis in a cell type specific manner in hepatocellular carcinoma cells
Author's Affiliation
Other Contributor(s)
Abstract
CD147/Basigin/EMMPRIN is overexpressed in several cancerous tissues and it has been shown to induce matrix metalloproteinases (MMPs) whose expression is associated with cancer metastasis. Thus, targeting CD147 with monoclonal antibodies (mAbs) potentially has therapeutic applications in cancer immunotherapy. Here, we report the use of anti-CD147 mAbs targeting domain 1 of CD147, namely M6-1D4 (IgM), M6-1F3 (IgM), M6-2F9 (IgM) and M6-1E9 (IgG2a), against several human cancer cell lines. Strikingly, IgM but not IgG mAbs against CD147, especially clone M6-1D4, induced acute cellular swelling, and this phenomenon appeared to be specifically found with hepatocellular carcinoma (HCC) cells. Furthermore, molecular investigation upon treating HepG2 cells with M6-1D4 showed unfolded protein response (UPR) activation, autophagosome accumulation, and cell cycle arrest, but without classic apoptosis related features. More interestingly, prolonged M6-1D4 treatment (24 h) resulted in irreversible oncosis leading to necroptosis. Furthermore, treatment with a mixed lineage kinase domain-like psuedokinase (MLKL) inhibitor and partial knockout of MLKL resulted in reduced sensitivity to necroptosis in M6-1D4-treated HepG2 cells. Surprisingly however, the observed necroptotic signaling axis appeared to be non-canonical as it was independent of receptor-interacting serine/threonine-protein kinase (RIPK) phosphorylation. In addition, no cytotoxic effect on human dermal fibroblast (HDF) was observed after incubation with M6-1D4. Taken together, this study provides clues to target CD147 in HCC using mAbs, as well as sheds new light on a novel strategy to kill cancerous cells by the induction of necroptosis.