The
opioid growth factor (OGF) regulates cell proliferation of human
cancer cells through the
cyclin-dependent kinase inhibitory pathway, with mediation of this action by the
OGF receptor (OGFr). The ubiquity of the OGF-OGFr axis in human
cancer is unknown. We used 31 human
cancer cell lines, representative of more than 90% of
neoplasias occurring in humans, and found that OGF and OGFr were detected in the cytoplasm and nucleus by immunohistochemistry. The addition of OGF to cultures depressed cell number up to 41%, whereas
naltrexone (NTX) increased cell proliferation by up to 44%, a total of 85% in the modulating capacity for the OGF-OGFr axis. Neutralization of OGF by specific
antibodies led to a marked increase in cell number. Knockdown of OGFr by OGFr-
siRNA resulted in a significant increase in the number of cells, even in the face of the addition of exogenous OGF. The cultures to which NTX was added and subjected to OGFr-
siRNA were similar to those with OGF-
siRNA alone. The OGF-OGFr axis, a physiological determinant of cell-proliferative activity, is a ubiquitous feature of human
cancer cells. The identification of this native
biological system in
neoplasia may be important in understanding the pathophysiology of
neoplasia, and in designing treatment modalities that utilize the body's own chemistry.