Histamine Regulates MDA MB 231 Breast Cancer Cell Line Invasive Potential.

GRACIELA P CRICCO, MARÍA S SÁEZ, NORA A MOHAMAD, EDUARDO VALLI, ROSA M BERGOC, ELENA S RIVERA, GABRIELA A MARTÍN.

Durham, England.

Congreso; European Histamine Research Society. XXXIX Meeting.; 2010

European Histamine Research Society

We have previously demonstrated that MDA MB 231, a metastatic breast cancer cell line, expresses the four known types of histamine receptors which differentially regulate cell proliferation. We have also determined that histamine increases MDA MB 231 cells intrinsic sensibility to ionizing radiation. The aim of the present study was to investigate the role of histamine in cellular events involved in metastatic capacity, such as expression and activity of matrix metalloproteinases (MMPs), cell migration and invasion. The possible interaction between histamine treatment and irradiation was also evaluated since ionizing radiation may affect metastatic competence depending upon cell type and irradiation characteristics. Histamine in concentration over 10 uM decreased MMP2 and MMP9 expression assessed by RT-PCR and cytochemistry as well as enzymatic activity determined by zymography. This effect was mimicked by H2 agonist amthamine, while an opposite action was observed when H4 agonist VUF 8430 was employed. Experiments using transwell systems demonstrated that 1uM histamine increases cell migration, though concentrations higher than 10 uM decreased migration. Also, wound healing assays showed that cell motility was significantly augmented via H4 receptors, though diminished through H2 receptors. In addition, assays employing matrigel coated tranwells showed that histamine enhanced MDA MB 231 cells invasion ability via H4 receptors. Cells irradiated with a 2 gray Dose showed a rise in metalloproteinases activity and cell motility compared to control cells; however this effect was counteracted by histamine treatment. In summary, histamine differentially regulates expression and activity of matrix metalloproteinases, cell migration and invasiveness through H2 and H4 receptors in MDA MB 231 cells. Results also suggest that histamine could improve radiotherapy efficacy regarding the potential development of metastases.