N-Glycosylation of ß4 Integrin Controls the Adhesion and Motility of Keratinocytes

α6ß4 integrin is an essential component of hemidesmosomes and modulates cell migration in wound healing and cancer invasion. To elucidate the role of N-glycosylation on ß4 integrin, we investigated keratinocyte adhesion and migration through the re-expression of wild-type or N-glycosylation-defective ß4 integrin (ΔNß4) in ß4 integrin null keratinocytes. N-glycosylation of ß4 integrin was not essential for the heterodimer formation of ß4 integrin with α6 integrin and its expression on a cell surface, but N-glycosylation was required for integrin-mediated cell adhesion and migration. Concomitantly with the reduction of ß4 integrin in the membrane microdomain, the intracellular signals of Akt and ERK activation were decreased in cells expressing ΔNß4 integrin. Forced cross-linking of ß4 integrin rescued the decreased ERK activation in ΔNß4 integrin-expressing cells to a similar extent in wild-type ß4 integrin-expressing cells. Surprisingly, compared with cells expressing wild-type ß4 integrin, an alternation in N-glycan structures expressed on epidermal growth factor receptor (EGFR), and the induction of a stronger association between EGFR and ß4 integrin were observed in ΔNß4 integrin-expressing cells. These results clearly demonstrated that N-glycosylation on ß4 integrin plays an essential role in keratinocyte cellular function by allowing the appropriate complex formation on cell surfaces

The enhanced expression of the matrix metalloproteinase 9 in nasal NK/T-cell lymphoma

<p>Abstract</p> <p>Background</p> <p>Nasal NK/T cell lymphoma is an aggressive disease and has a poor prognosis. Nasal NK/T cell lymphoma is refractory to conventional chemotherapy and has strong tendency of widespread relapse or dissemination into distant sites.</p> <p>Methods</p> <p>We immunohistochemically studied nasal NK/T-cell lymphoma to elucidate the unique characteristics of nasal NK/T-cell lymphoma, such as its higher metastatic tendency and its vast necrosis which leads to destruction of the involved tissues. The expression of P-glycoprotein and MMP-9 was evaluated in the 20 patients with nasal NK/T-cell lymphoma and 25 with nasal non-NK/T-cell lymphoma and the relationship between expression of these proteins and clinical results were analyzed in this report.</p> <p>Results</p> <p>Overall 5-year survival rates for patients with nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were 51%, and 84%. Distant involvement free 5-year survival rates for patients with nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were 53%, and 79%.</p> <p>Overall positivity for P-glycoprotein was observed in 10 of 19 patients with NTL and in 13 of 23 patients with non-NTL. When the overall survival rate was compared between patients with P-glycoprotein positive and negative, there was no difference between them.</p> <p>Sixteen of the 19 patients with nasal NK/T cell lymphoma expressed MMP-9. In contrast, only 8 of the 22 patients with nasal non-NK/T cell lymphoma expressed MMP-9. Distant involvement free 5-year survival rates for patients with MMP-9 negative, and MMP-9 positive were 92%, and 61%, respectively. The difference was statistically significant (p = 0.027).</p> <p>Conclusion</p> <p>Positive immunoreactivity for P-glycoprotein was not an independent prognostic factor in nasal NK/T-cell lymphomas, which stresses the importance of exploring other mechanisms of drug resistance. The strong expression of MMP-9 is uniquely characteristic of nasal NK/T cell lymphoma and may contribute to its strong tendency to disseminatate and the extensive necrosis which is always seen. However, our results are based on univariate comparisons, and as such, should be viewed with some caution.</p

Basement membrane components are key players in specialized extracellular matrices

More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches