Mast cells infiltration in premalignant tongue lesions upon TTP ablation in conditional transgenic mice.

DARIO M FERRI; EDITH KORDON; VALERIA SANCHEZ; ANA R RAIMONDI; MARINA AYRE; MARIA L PAPARELLA

Mar del Plata

Congreso; LXIV Reunion Anual de la Sociedad Argentina de Investigación Clínica(SAIC); 2019

SAIC

Oral squamous cell carcinoma (SCC) is the sixth most common cancer worldwide and tongue SCC is the most common malignancy of the oral cavity. RNA-binding proteins (RNA-BP) that regulate the stability of transcripts play a key role in disease pathogenesis. Tristetraprolin (TTP) is a RNA-BP that regulates proinflammatory mediators which promote tumorigenesis. We have previously developed a TTP knock out mice for oral cavity (TTP-KO: K14-CreERtam/TTP-/-). TTP-KO mice developed dysplastic lesions in the tongue accompanied with inflammatory cells infiltration in the dermis. Moreover, by breeding the TTP-KO mice with transgenic mice for K-rasG12D, we obtained compound mice (K14-CreERtam/TTP-/-/K-rasG12D+/-) that developed a complete oral phenotype, a reduced survival time, more aggressive histologic features and persistent inflammatory infiltrate. Compound mice heterozygous for TTP showed a different phenotype (het-compound mice). To study the inflammatory infiltrate in these premalignant lesions we characterize their cell composition. We performed immunohistochemistry for S100A (monocytes, neutrophils, macrophages) and 2 different stainings with alcian blue- safranin (AB-S) and toluidine blue (TB) for mast cells. We found S100A positives cells in the tongues of TTP-KO, compound and het-compound mice. The S100A cells were distributed equally between groups. Besides, we found AB-S positives cells in the connective tissue of the tongues in all experimental groups. However the distribution and amount of these cells were not homogenous. We performed TB staining and quantified positives cells (cell/area dermis). We found a statistically significant increase in TB positives cells in TTP-KO (19.8 ±1.8) compared with compound (11.04± 2.01), het compound (6.26 ±1.21) and wild type tongues (10.68±4.27) ANOVA p