ABSTRACT
BACKGROUND: Oral squamous cell carcinoma is characterized by high degree of local invasion with metastasis as well as characteristic angiogenic features. Angiogenesis is a critical step in the growth and metastasis of tumors. Cluster of differentiation 44 (CD44) is a cell surface glycoprotein which is widely expressed in both physiological and pathological conditions. AIM: The study was designed to assess the expression of CD44 (NKI-P1) in oral squamous cell carcinoma associated endothelial cells and to correlate this expression with matrix metalloprpteinase-9 (MMP-9) and transforming growth factor-beta (TGF- ß) expression immunohistochemically. MATERIALS AND METHODS: One hundred fourteen archival oral squamous cell carcinoma cases were used in this study. Immunohistochemistry was performed for CD44 (NKI-P1), Ki-67, cluster of differentiation 31(CD31), podoplanin (D2-40), MMP-9 and TGF- ß. Microvessel density was also determined morphologically. Results: CD44 was expressed in (CD31+/ Podoplanin -) blood vascular endothelial cells in a strong cytoplasmic fashion. In addition, the extracellular matrix proteins (MMP-9 and TGF-ß were expressed in oral squamous cell carcinoma stroma which was enriched with CD44 + blood vessels. The mean numbers of microvessel density in connective tissue beneath normal epithelium and different grades of oral squamous cell carcinoma stroma were 5.8, 22.1, 22.4 and 23.5, respectively with the P-value < 0.05, where a significant statistical difference between microvessel density in the connective tissue beneath normal epithelia and stroma of all grades of oral squamous cell carcinoma was found. Conclusion: CD44 (NKI-P1) is considered a potential marker of oral squamous cell carcinoma angiogenesis and it can be used as a valuable biomarker of tumor invasion and as a therapeutic target for anti-angiogenic therapies.
ABSTRACT
BACKGROUND: Periostin, IFN-induced transmembrane protein 1 (IFITM1) and Wingless-type MMTV integration site family, member 5B (Wnt-5b) were previously identified as the invasion promoted genes of head and neck squamous cell carcinoma (HNSCC) by comparing the gene expression profiles between parent and a highly invasive clone. We have previously reported that Periostin and IFITM1 promoted the invasion of HNSCC cells. Here we demonstrated that Wnt-5b overexpression promoted the invasion of HNSCC cells. Moreover, stromelysin-2 (matrix metalloproteinase-10; MMP-10) was identified as a common up-regulated gene among Periostin, IFITM1 and Wnt-5b overexpressing HNSCC cells by using microarray data sets. In this study, we investigated the roles of MMP-10 in the invasion of HNSCC. METHODS AND FINDINGS: We examined the expression of MMP-10 in HNSCC cases by immunohistochemistry. High expression of MMP-10 was frequently observed and was significantly correlated with the invasiveness and metastasis in HNSCC cases. Next, we examined the roles of MMP-10 in the invasion of HNSCC cells in vitro. Ectopic overexpression of MMP-10 promoted the invasion of HNSCC cells, and knockdown of MMP-10 suppressed the invasion of HNSCC cells. Moreover, MMP-10 knockdown suppressed Periostin and Wnt-5b-promoted invasion. Interestingly, MMP-10 overexpression induced the decreased p38 activity and MMP-10 knockdown induced the increased p38 activity. In addition, treatment with a p38 inhibitor SB203580 in HNSCC cells inhibited the invasion. CONCLUSIONS: These results suggest that MMP-10 plays an important role in the invasion and metastasis of HNSCC, and that invasion driven by MMP-10 is partially associated with p38 MAPK inhibition. We suggest that MMP-10 can be used as a marker for prediction of metastasis in HNSCC.
