Histamine Modulates Cellular Events Involved in Tumor Invasiveness in Pancreatic Carcinoma Cells

CRICCO GRACIELA; NUÑEZ MARIEL; MEDINA VANINA; GARBARINO GLORIA; MOHAMAD NORA; GUTIERREZ ALICIA; COCCA CLAUDIA; KIRCHHEIMER R; BERGOC ROSA; RIVERA ELENA; MARTIN GABRIELA

Mayo 11-14, 2005, Bled, Eslovenia.

Congreso; European Histamine Research XXXIV Annual Meeting,; 2005

Histamine Modulates Cellular Events Involved in Tumor Invasiveness in Pancreatic Carcinoma Cells. Graciela Cricco, Mariel Núñez, Vanina Medina, Gloria Garbarino, Nora Mohamad, Alicia Gutiérrez, Claudia Cocca, Carolina Kirchheimer, Rosa Bergoc, Elena Rivera, Gabriela Martín. Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, 1113,  Buenos Aires, Argentina. Progression of metastatic epithelial tumors is characterized by an increased  motility, a decrease in cellular adhesion, high expression and activation of metalloproteases (MMP) and high angiogenesis capability. In the human pancreatic carcinoma cell line PANC-1, histamine (HA) acts as a growth factor modulating cellular proliferation via H1 and H2 histamine receptors. The objective of this work was to study HA action on cellular adhesion and migration and the expression of MMPs in this cell line. Methylene blue staining of formaline fixed cells, between 30 and 60 minutes after seeding, was performed for studying cellular adhesion. Cells had been previously treated with HA for 48 hours. A decrease in the adhesion to plastic was seen at any tested time. At 90 minutes: Control 100%, 10 mM HA = 63%, 10 nM HA = 44%, ANOVA p<0.01. The scratch wound healing technique was used to evaluate cellular migration. PCNA expression was determined by flow cytometry, in order to discard cellular division. It was observed an increased motility in 10 nM HA treated cultures after 24 hours, whereas there was no difference in PCNA expression between treated and control. MMP-2 and MMP-9 activities were determined by zymography. The intensity of gelatinolytic bands was quantified by an appropriate software and results were expressed as a percentage of control values. It was determined an increase in the active form of MMP-2 in the supernatants of HA 10nM treated cultures (130% vs control 100%, Student’s test p< 0.05). Present data indicate that HA could be involved in tumoral progression towards metastasis in PANC-1 cell line.