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In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
Published on: May 4, 2017
Mortalin inhibitors sensitize K562 leukemia cells to complement-dependent cytotoxicity
David Pilzer1, Moran Saar, Keizo Koya
1Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
International Journal of Cancer
|September 10, 2009
Summary
Mortalin, a heat shock protein, helps cancer cells resist complement attacks. Inhibiting mortalin increases cancer cell death, suggesting it as a new immunotherapy target.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Mortalin (mitochondrial hsp70) is overexpressed in cancers, correlating with poor prognosis.
- Cancer cells resist complement-dependent cytotoxicity by removing the membrane attack complex (MAC).
- Mortalin and MAC are released in vesicles from complement-attacked cells.
Purpose of the Study:
- To investigate mortalin's role in cancer cell resistance to complement-dependent cytotoxicity.
- To evaluate mortalin inhibition as a strategy to enhance anti-cancer therapies.
Main Methods:
- Knockdown of mortalin using siRNA.
- Treatment with MKT-077, a mortalin-inhibiting dye.
- Assessing cell sensitivity to MAC-induced cell death.
- Analyzing MAC-mortalin vesiculation and C9 binding.
Main Results:
- Mortalin knockdown and MKT-077 treatment reduced MAC elimination and increased cell death.
- MKT-077 sensitized cells to MAC-mediated lysis but not streptolysin O.
- MKT-077 inhibited MAC-mortalin vesiculation and mortalin's binding to C9.
- Mortalin's effect on complement lysis was independent of p53 status.
Conclusions:
- Mortalin promotes cancer cell survival against complement-dependent cytotoxicity.
- Targeting mortalin could be a novel strategy for cancer adjuvant immunotherapy.
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