Toll-like receptors -4 and -5 in oral and cutaneous squamous cell carcinomas.

BACKGROUND: Oral squamous cell carcinoma (OSCC) has a worse prognosis than cutaneous squamous cell carcinoma (CSCC). Toll-like receptor- 4 (TLR-4) and TLR-5 are transmembrane proteins that recognize endogenous and microbial agents. Their activation has been connected to cancer invasion. OBJECTIVE: The aim was to study the expression of TLR-4 and TLR-5 in OSCC and CSCC samples, and the effects of TLR-5 ligand flagellin on the proliferation, migration, and invasion of different mucocutaneous cell lines in vitro. METHODS: Samples of early-stage tumors (T1-T2N0M0) from 63 patients with OSCC and CSCC were obtained, in addition to eight normal mucosa and skin tissues from healthy subjects. Oral-cavity-derived highly aggressive HSC-3, less invasive SAS, and HPV-transformed benign IHGK as well as C-ha-ras-transformed (HaCat) skin carcinoma II-4 and non-invasive A5 cell lines were used. Flagellin-induced mucocutaneous cell lines were compared by using BrdU-proliferation, scratch migration, and myoma organotypic invasion assays. RESULTS: TLR-4 expression was similar in OSCC and CSCC tumors. TLR-5 was more abundant in OSCC than in CSCC samples. Flagellin induced the proliferation of SAS, II-4 and A5, migration of IHGK, II-4 and A5, and the invasion of II-4 cells. It had no effect on HSC-3 cells. CONCLUSIONS: Flagellin, a TLR-5 agonist, induced the migration and invasion of less aggressive mucocutaneous cell lines, but it had no effect on the most invasive oral carcinoma cells. The more aggressive clinical behavior of OSCC compared to CSCC may partially be related to the differences in the expression of TLR-5 in these malignancies.

Epithelial and stromal syndecan-1 and -2 are distinctly expressed in oral- and cutaneous squamous cell carcinomas.

BACKGROUND: Oral squamous cell carcinoma (OSCC) and cutaneous squamous cell carcinoma (CSCC) are epithelial neoplasms of which OSCC has worse survival and higher risk of metastasis than CSCC. The aim of this study was to explore the differences of immunoexpressions between syndecan-1 and -2 in OSCC and head and neck CSCC. METHODS: A total of 35 patients diagnosed with OSCC and 25 with CSCC, presented T1 and T2 tumors and treated at Helsinki University Central Hospital between years 2001 and 2009, were selected into this study. The levels and locations of syndecan-1 and -2 immunostainings were analyzed using formalin-fixed and paraffin-embedded tissue samples of OSCC and CSCC cases together with clinical data. RESULTS: Cell membrane epithelial syndecan-1 expression decreased significantly compared to normal tissue in both cancer types. Cell membrane syndecan-1 expression in the invasive front had negative correlation with invasion depth of both tumors (OSCC, r = -0.339, P = 0.025; CSCC, r = -0.469, P = 0.004). In cancers over 4-mm invasion depth, the number of stromal syndecan-1-positive collagen fibers and inflammatory cells were higher in OSCC than in CSCC. Syndecan-2 expression in non-malignant stroma was higher in CSCC than in OSCC tumors. In addition, unlike syndecan-1, syndecan-2 was more often and more intensively expressed in the tumor inflammatory cells in CSCC than in OSCC. CONCLUSION: Our results suggest that variable stromal expression of syndecan-1 and -2 in OSCC compared to CSCC may at least partially explain the differences in their clinical behavior.