M-CSF gene transduction in multidrug-resistant human cancer cells to enhance anti-P-glycoprotein antibody-dependent macrophage-mediated cytotoxicity.

Abstract

A human macrophage-colony-stimulating-factor (M-CSF) gene inserted into an expression vector (pRc/CMV-MCSF) was transfected into multidrug-resistant (MDR) human ovarian cancer cells (AD10) to induce secretion of human M-CSF into the medium. The M-CSF level in the culture medium of the transfected cells reached 100 ng/ml after 7 days, and the ability of the cells to secrete M-CSF was stable for at least 3 months. Transfection of the M-CSF gene did not result in any change in expression of MDRI (P-glycoprotein), proliferation or chemosensitivity of the cells from those of the parent cells. There was also no difference between the transfected and the parent cells in susceptibility to NK cell- or interleukin-2-activated killer-cell-mediated cytotoxicity. Human blood monocytes that had been incubated for 4 days in medium with the culture supernatant of MH-AD10 cells exhibited higher ADCC activity than untreated monocytes against MDRI-positive cancer cells. This effect of the supernatant of AD10 cells was completely abolished by its treatment with a monoclonal anti-M-CSF antibody (MAb). When transfected human MDR cells were injected into nude mice, an inverse correlation was seen between the ability of the cells to produce M-CSF and their tumorigenicity. Thus, gene modification of MDR cancer cells seems hopeful as a therapeutic method for enhancing anti-MDRI-MAb-dependent macrophage-mediated cytotoxicity against human MDR cancer cells.

• Authors: Y Heike, S Sone, S Yano, H Seimiya, T Tsuruo, T Ogura
• Journal: International journal of cancer (Int J Cancer) Vol. 54 Issue 5 Pg. 851-7 (Jul 09 1993) ISSN: 0020-7136 [Print] United States
• PMID: 8100809 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Carrier Proteins
• Membrane Glycoproteins
• Macrophage Colony-Stimulating Factor

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Animals
• Antibody-Dependent Cell Cytotoxicity (genetics, immunology)
• Carrier Proteins (immunology)
• Cell Division
• Cells, Cultured
• Drug Resistance (genetics, immunology)
• Female
• Humans
• Lymphocytes (immunology)
• Macrophage Colony-Stimulating Factor (biosynthesis, genetics)
• Macrophages (immunology)
• Membrane Glycoproteins (immunology)
• Mice
• Mice, Nude
• Monocytes (immunology)
• Neoplasm Transplantation
• Ovarian Neoplasms (genetics, immunology, pathology, therapy)
• Transfection