Oral (OSCC) and cutaneous (CSCC) squamous cell carcinomas are epithelial neoplasms, which are both derived from keratinocyte cells. However, the etiology and prognosis of OSCC and CSCC are different. The main etiological factors behind OSCC are tobacco smoke and alcohol consumption, and for CSCC it is UV-radiation. OSCC has poorer prognosis than CSCC. In order to be invasive, cancer cells have to pass various barriers. They have to disrupt cell-to-cell junctions, penetrate basement membranes, and invade connective tissue. The pattern of invasion of tumors varies strikingly. Some invade in large border fronts while others invade in single cell manner. Expression of the transmembrane proteins, E-cadherin and syndecan-1, in cell membrane are lost during tumor invasion, and therefore loosening cell adhesion. Matrix metalloproteinases (MMP) are tissue proteinases, which have a proteolytic role in various physiological events and during tumor progression MMPs are capable of degrading extracellular matrix (ECM) proteins but also have an immunomodulatory role. Toll-like receptors (TLRs) are part of the innate immunity and can recognize exogenous pathogen associated molecular patterns or endogenous damage associated molecular patterns. Cancer cells may use TLRs to induce tumor-promoting inflammation. The aim of the study was to examine possible cellular and molecular differences between OSCC and CSCC explaining their different behaviors as cancers despite having cellular similarities. The study included 36 OSCC and 27 CSCCs from patients with early stage histological risk assessment (HRA) model and histological risk assessment score (HRS). We performed immunohistochemical staining for E-cadherin, Snail (Snail1), Syndecans (1 and 2), MMPs (7, 8 and 9) and TLRs (4 and 5). In vitro, with oral and cutaneous cell lines the effect of TLR-5 ligand flagellin on proliferation, migration and invasion was studied. OSCC patients had worse disease-specific survival than CSCC patients and this correlated with the invasion depths of the OSCC tumors. OSCC had a more severe histological pattern of invasion than CSCC. E-cadherin and Syndecan-1 expression decreased in the invasive front of OSCCs and CSCCs. Syndecan-1 expression in the tumor stroma was higher in OSCC than in CSCC in tumors with invasion depth over 4 mm. MMP-7 was mainly expressed in the invasive front of OSCC and CSCC and was stronger in OSCC than in CSCC. MMP-8 and MMP-9 were mainly expressed in the peritumoral inflammatory cells. TLR-5 expression was stronger in OSCC than in CSCC. In vitro, TLR-5 ligand flagellin increased proliferation, migration and invasion of less aggressive oral and cutaneous cell lines, but failed to do so with the most aggressive oral cancer cell line. In conclusion, the OSCC patients of this study had poorer disease specific survival than CSCC patients. Increased stromal syndecan-1 expression in OSCC, MMP-7 expression in the invasive front of the tumor, and MMP-9 expression in inflammatory cells could partly explain the differences in survival between OSCC and CSCC.
|Tila||Julkaistu - 2015|
|OKM-julkaisutyyppi||G5 Tohtorinväitöskirja (artikkeli)|
- 313 Hammaslääketieteet