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Binding of opioids to human MCF-7 breast cancer cells and their effects on growth
R Maneckjee1, R Biswas, B K Vonderhaar
1NCI Navy Medical Onocology Branch, Bethesda Naval Hospital, Maryland 20814.
Abstract:
The well characterized human breast cancer cell line, MCF-7, has been shown to possess membrane receptors for various opioid ligands, and these compounds have been shown to modulate the growth of the cells in culture. Using specific radioligands for the receptor types, we were able to demonstrate that the MCF-7 cells possess multiple opioid receptor types. Relatively high-affinity-binding sites are present for the mu- and kappa-specific ligands, while lower affinity sites are present for the delta-agonist. Opioid ligands specific for the different receptor types significantly inhibited the growth of the MCF-7 cells in a dose-dependent manner when grown in the presence of 10% fetal bovine serum. This inhibitory effect was reversed by the simultaneous administration of the opioid receptor antagonist, naloxone. However, the opioid effect appears to be restricted to the hormonally responsive fraction of the MCF-7 cell growth. Cells grown in the presence of charcoal-stripped fetal bovine serum are refractory to the effects of the opioids unless the media is supplemented with estradiol. The data presented here suggest an important regulatory role for opioids in the growth and development of human breast cancers.
Insights
Opioid receptors on human breast cancer cells (MCF-7) influence their growth. Opioid ligands inhibit cell proliferation, an effect dependent on hormonal signaling and reversed by naloxone.
Area of Science:
- Oncology
- Neuroendocrinology
- Molecular Pharmacology
Background:
- The human breast cancer cell line MCF-7 expresses membrane receptors for opioid ligands.
- Opioid compounds have demonstrated the ability to modulate the growth of these cancer cells in vitro.
Purpose of the Study:
- To investigate the presence and types of opioid receptors on MCF-7 cells.
- To determine the effect of specific opioid ligands on MCF-7 cell proliferation.
- To explore the role of hormonal responsiveness in opioid-mediated effects on breast cancer cell growth.
Main Methods:
- Utilized specific radioligands to identify and characterize multiple opioid receptor types (mu, kappa, delta) on MCF-7 cells.
- Assessed the impact of opioid ligands on cell growth in the presence of standard and charcoal-stripped fetal bovine serum.
- Investigated the reversal of opioid effects using the opioid receptor antagonist naloxone and estradiol supplementation.
Main Results:
- MCF-7 cells possess high-affinity binding sites for mu- and kappa-specific opioid ligands and lower affinity sites for delta-agonists.
- Opioid ligands significantly inhibited MCF-7 cell growth in a dose-dependent manner.
- The inhibitory effect of opioids was dependent on hormonal signaling, being reversed by naloxone and requiring estradiol supplementation in stripped serum.
Conclusions:
- Opioid receptors are present on MCF-7 human breast cancer cells.
- Opioid ligands can regulate the growth of these cells, particularly the hormonally responsive fraction.
- Opioids may play a significant role in the growth and development of human breast cancers.