Abstract 3278: Dopamine inhibits growth of multiple myeloma

Abstract

Abstract Introduction: Multiple myeloma (MM), progressive plasma cell tumor leading to overproduction of monoclonal immunoglobulins, osteolytic bone lesions, renal disease and immunodeficiency, is the second most prevalent hematologic malignancy in the United States. Vascular endothelial growth factor-A (VEGF-A) is a critical cytokine responsible for the induction of angiogenesis in several solid and hematological malignancies like MM. It is likely that VEGF-A induced bone marrow (BM) angiogenesis promotes the survival, growth and proliferation of MM .Therefore targeting BM angiogenesis in MM may be effective for the treatment of MM patients Objective/Hypothesis: Bone marrow stromal cells (BMSC) are believed to play a central role in progression of MM pathogenesis. Along with other factors, these cells overproduce IL-6 that in turn stimulates growth, survival and progression of MM cells. Since it has been shown that VEGF-A can stimulate IL-6 secretion by these cells and because we have demonstrated that neurotransmitter dopamine (DA) can inhibit VEGF-A functions by acting through its D2 receptors (D2R) and BMSC express DAD2R, we therefore hypothesize that DA or D2R agonists have a role in inhibiting VEGF-A mediated IL-6 secretion by BMSC and thereby, MM progression. Results: Our results indicate that VEGF-A can significantly increase the secretion of IL6 by isolated BMSC cells in vitro. Addition of DA or D2R agonist, quinpirole, to VEGF-A treated BM cells results in suppression of IL-6 production. However treatment with D2R antagonist, eticlopride, prior to treatment with DA results in abrogation of the effect of DA. Similar effects of DA on VEGF-A induced IL-6 secretion was also observed in HS-5 human BM stromal cells. Our results further indicate that VEGF-A induced VEGFR1 phosphorylation is suppressed in HS-5 cells on treatment with D2R agonist. Furthermore, DA also inhibits the proliferation of MM1.S human MM cells in vitro. Conclusion: DA may be a new and an effective approach to retard the progression of MM. Since anti-angiogenic monotherapy cannot eradicate the disease completely, strategies using DA with more traditional modalities to eradicate the disease at the time of initial treatment might be beneficial. Finally, DA or its D2R agonists are being used in the clinics for several years for the treatment of other disorders, therefore these inexpensive drugs (in comparison to presently available drugs for the treatment of MM) with known and manageable side effects can be used in the clinics in near future for the treatment of both early and late stage MM. Citation Format: Chandrani Sarkar, Debanjan Chakroborty, Sujit Basu. Dopamine inhibits growth of multiple myeloma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3278.