Histamine receptor 2 blockade reduces breast tumor development and metastasis (TUM9P.1010)

Abstract

Abstract Histamine has multiple immunomodulatory roles that impact innate and acquired immunity. Histamine receptor antagonists are widely used clinically to treat allergic disease and gastrointestinal disorders, but their ability to alter effective immune function to breast tumors is unknown. We hypothesized that histamine receptor antagonist treatment could alter immune function in mouse models of breast cancer, therefore altering the growth and spread of breast cancer. Two injectable breast tumor models (the 4T1-BALB/c and E0771-C57BL/6 model) and a spontaneous breast cancer model (STK-/-/NIC model) were utilized. Histamine receptor antagonists were administered in the drinking water prior to tumor cell injection or at time of weaning, respectively. The immune cell populations in the spleen and bone marrow of tumor-bearing mice were analyzed. Ranitidine and famotidine (Hrh2 antagonists) but not selective Hrh1 or Hrh4 antagonists significantly inhibited metastasis in the 4T1 model. Ranitidine treatment also caused significant primary tumor regression in the E0771 breast cancer model. In the STK-/-/NIC model, ranitidine increased latency and decreased the number of tumors per mouse at week 26. Bone marrow and spleen analysis revealed that oral ranitidine treatment significantly and selectively decreased monocyte populations. These studies suggest that HRH2 antagonists may have potential as a beneficial immunomodulatory agent in the prevention or treatment of breast cancer.