Reduced tumor growth, experimental metastasis formation, and angiogenesis in rats with a hyperreactive dopaminergic system.
Outgrowth of solid tumors requires blood supply to the tumor. Tumor angiogenesis is dependent on the interplay between tumor-derived angiogenic factors and stromal cells. Recently, it has been shown that the neurotransmitter dopamine is a potent inhibitor of VEGF-induced angiogenesis. Moreover, there is evidence that patients with schizophrenia have a hyperreactive dopaminergic system and are relatively protected from cancer. We hypothesized that hyperreactivity of the dopaminergic system is related to reduced angiogenesis and tumor development. Therefore, we investigated tumor growth and angiogenesis in two lines of Wistar rats with high (APO-SUS) or low (APO-UNSUS) dopaminergic reactivity. Subcutaneous implants of mammary adenocarcinoma cells (MADB106) in matrigel remained 35% smaller in APO-SUS rats than in APO-UNSUS rats (P<0.01). Moreover, APO-SUS rats developed less lung metastases after i.v. administration of MADB106 tumor cells. Furthermore, hemoglobin content (APO-SUS: 40.6+/-7.6; APO-UNSUS: 76.9+/-13 mg/dl, P<0.05) and expression of the endothelial determinant PECAM-1 in tumors from APO-SUS rats were reduced (APO-SUS: 37+/-18; APO-UNSUS 69+/-25 units, P<0.01), indicating that reduced angiogenesis is responsible for reduced tumor development in APO-SUS rats. These results suggest a novel link between dopaminergic reactivity, angiogenesis, and tumor development and may explain part of the individual differences in cancer progression.
Laboratory for Psychoneuroimmunology, University Medical Center Utrecht, The Netherlands.
Marc A T
MA
Teunis
Annemieke
A
Kavelaars
Emile
E
Voest
Joost M
JM
Bakker
Bart A
BA
Ellenbroek
Alexander R
AR
Cools
Cobi J
CJ
Heijnen
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003094:Collagen; D017077:Culture Media, Conditioned; D004298:Dopamine / Q000378:metabolism*; D004338:Drug Combinations; D006133:Growth Substances / Q000502:physiology; D007797:Laminin; D008175:Lung Neoplasms / Q000556:secondary; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000097:blood / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D018919:Neovascularization, Physiologic; D011509:Proteoglycans; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D017077:Culture Media, Conditioned; D004338:Drug Combinations; D006133:Growth Substances; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D004298:Dopamine