Y. Heike et al., M-CSF GENE TRANSDUCTION IN MULTIDRUG-RESISTANT HUMAN CANCER-CELLS TO ENHANCE ANTI-P-GLYCOPROTEIN ANTIBODY-DEPENDENT MACROPHAGE-MEDIATED CYTOTOXICITY, International journal of cancer, 54(5), 1993, pp. 851-857
A human macrophage-colony-stimulating-factor(M-CSF) gene inserted into
an expression vector (pRc/CMV-MCSF) was transfected into multidrug-re
sistant (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. Trans
fection of the M-CSF gene did not result in any change in expression o
f MDRI (P-glycoprotein), proliferation or chemosensitivity of the cell
s 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 bloo
d monocytes that had been incubated for 4 days in medium with the cult
ure supernatant of MH-AD10 cells exhibited higher ADCC activity than u
ntreated monocytes against MDRI -positive cancer cells. This effect of
the supernatant of AD10 cells was completely abolished by its treatme
nt with a monoclonal anti-M-CSF antibody (MAb). When transfected human
MDR cells were injected into nude mice, an inverse correlation was se
en between the ability of the cells to produce M-CSF and their tumorig
enicity. 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. (C) 1993 Wiley-L
iss, Inc.