Abstract 183: Beta-endorphin neuron transplants suppress mammary tumor growth and progression: role of immune cells.

Abstract

Abstract We have recently identified that a set of hormone secreting nerve cells in the hypothalamus, called beta-endorphin (BEP) neurons, have the ability to prevent the growth, progression and metastasis of mammary and prostate tumors in laboratory animals. How these neuronal cells prevent tumor cell growth and progression is not apparent. In order to better understand the mechanism by which endorphin neurons control tumor growth, we determined the growth and clearance of breast cancer derived MADB106 cells in Fisher rats, which are immune intact, and in athymic Nude rats, which are T cells deficient. Adult female Fischer rats or Nude rats were transplanted with either BEP neurons or cortical neurons (control) in the hypothalamus for 4 weeks and then inoculated with MADB106 cells in the jugular vein or under the skin in the back. These animals were sacrificed after 6 weeks to determine the volume of the tumor at the site of inoculation for determining the growth of tumors and the number of other tumors at the distant sites for determining tumor metastasis. Tumors were also collected for histopathology. Blood samples were collected and used for measurements of cytokines and immune cells. In Fischer rats, after tumor inoculation, animals with control cell transplants had tumor colonization in the lung and some on the skin at the site of cell injection. However, BEP neurons treated Fischer rats had no tumor colonization in the body. In the Nude rats, tumor colonization occurred both at the site of injection and at the distant site under the skin as well as in the lung of control transplanted rats. In BEP neurons transplanted Nude rats, tumor colonization only occurred at the site of inoculation. The mean volume of tumor at the inoculation site was smaller in BEP neurons transplanted rats than in control cells transplanted rats. In BEP neurons transplanted rats, corticosterone and inflammatory cytokines levels were lower, whereas anti-inflammatory cytokines and chemokines levels were higher. In addition, NK cell and macrophage cell numbers and their cytolytic functions in peripheral blood of BEP neurons transplanted rats were elevated. These data suggest that the antitumor action of BEP neuron transplants is due to the activation of primarily NK cells and macrophages and also in lesser extent T cells. The data also identify the potential use of BEP cell therapy for cancer prevention. (Supported by R37 AA08757) Citation Format: Dipak K. Sarkar, Changqing Zhang, Sengottuvelan Murugan, Nadka Boyadjieva, María Ortigüela. Beta-endorphin neuron transplants suppress mammary tumor growth and progression: role of immune cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 183. doi:10.1158/1538-7445.AM2013-183