Functional Study Of KLK8 In Head And Neck Carcinoma

Ana STEFANINI, School of Medicine of São José do Rio Preto, Brazil

1 Department of Molecular Biology, School of Medicine of São José do Rio Preto, São José do Rio Preto, SP, Brazil

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. The median overall survival for patients with recurrent or metastatic lesions is low, despite recent advances in therapeutic techniques. The understanding of the molecular pathways involved in the initiation and progression of these tumors is therefore important not only for understanding their biology, but also for the development of effective therapeutic approaches. In our previous studies, the kallikrein 8 gene (KLK8) was observed differentially expressed in laryngeal carcinomas, suggesting its potential as a tumor marker. Kallikreins participate in proteolytic pathways that contribute to normal physiology and pathological conditions, modulating cell proliferation and survival and regulating angiogenesis, cell migration and invasion. The objective of the present study was to investigate the participation of the kallikrein 8 in the HNSCC development. The specific objectives included (a) to analyze the expression pattern of KLK8 and its most abundant variant in HNSCC, (b) to evaluate the effect of ectopic expression of KLK8 on HNSCC secretome, using proteomic and metabolomic approaches, and (c) to develop molecular homology modeling of protein KLK8. The results of gene expression analysis showed that the variant 1 of KLK8 has significantly reduced levels in HNSCC, unlike the other five variants. Its ectopic expression resulted in changes of cell morphology, increased proliferation, viability and migratory capacity, but no alterations in invasiveness. The data from cells with ectopic expression of KLK8 revealed small differences in their proteomes compared to control cells. Otherwise, these cells exhibited changes in their glycolytic pattern and in the effect of their secretome on the metabolism of other cells. For the first time, differences in expression of KLK8 variants and the effects of their ectopic expression were evaluated in HNSCC cells. Financial support: FAPESP, CNPq.