MAST CELL ACTIVATION AS A COLLABORATIVE MECHANISM IN THE GROWTH OF EXPERIMENTAL ORAL TUMORS.

AROMANDO R.; PÉREZ M. A.; RAIMONDI A. R.; ITOIZ M. E.

Atenas

Congreso; Congreso de la Academia Internacional de Patología; 2008

Academia Internacional de Patología

MAST CELL ACTIVATION AS A COLLABORATIVE MECHANISM IN THE GROWTH OF EXPERIMENTAL ORAL TUMORS. Aromando, RF, Pérez, MA, Raimondi, AR, Itoiz, ME Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Argentina, Oral and Pharyngeal Cancer Branch, NIH, Bethesda, MD, USA Background: Two effects on squamous cell carcinoma growth are currently attributed to mast cells, i.e. a direct action that involves the induction of proliferation of neoplastic cells and an indirect action that involves the induction of tumor angiogenesis. The induction of cell proliferation would be mediated by mast cell tryptase, capable of activating receptors PAR-2 (protease activated receptor-2) of the tumor cells and inducing their proliferation (Yoshii M. et al. 2005). In previous studies we demonstrated the association between mast cell activation and oral tumors cell proliferation in the hamster cheek pouch (Aromando; R. et al., in press). Feoktistov, I et al. (2003) described the potential mechanism of angiogenesis induction mediated by VEGF (vascular endothelial growth factor), secreted by human activated mast cells. The aim of the present study was to examine the potential correlation between mast cell activation in hamster cheek pouch tumors and the production of VEGF coupled to the ensuing increase in microvessels. Design: The right cheek pouch of Golden Syrian hamsters was submitted to a standard carcinogenesis protocol (Shklar G. et al, 1979) until tumor development. The hamsters were divided in two groups, i.e. control group: normal non-cancerized hamsters, and experimental group: hamsters with tumors. The animals were killed and the pouches were resected. The samples were processed for mast cell staining with Alcian Blue – Safranin (AB-S) to study different mast cell activation stages. Immunohistochemistry was performed for microvessel staining using Factor VIII and for demonstration of epithelial VEGF expression using anti-VEGF antibody. Mast cells and microvessels were counted in: tumor stroma, base of the tumor and in tissues of the cheek pouch wall. Mast cells were classified as AB (active) or S (inactive). Subjective evaluation of VEGF expression was performed based on the comparison with a human kidney standard. Results:  The total number of mast cells in the cheek pouch did not increase. However, an increase in active mast cells was detected at the base of the tumor. A correlation was established between this finding and an increase in vascular density (p < 0.001) and an increase in epithelial VEGF staining intensity. Conclusions: Mast cells would play a role in tumor angiogenesis via VEGF release in the hamster cheek pouch oral cancer model.