期刊
ORAL DISEASES
卷 27, 期 5, 页码 1137-1147出版社
WILEY
DOI: 10.1111/odi.13640
关键词
blocking antibody; Cripto-1; inhibitory peptide; Nodal; oral squamous cell carcinoma; therapeutic targets
资金
- Regione Campania
- Midwestern University
The study found that both Nodal and CR-1 are expressed in human oral squamous cell carcinoma, with Nodal intensity correlated with advanced-stage disease. Simultaneous treatment with Nodal and CR-1 inhibitors reduced cell viability and invasiveness, indicating therapeutic potential in targeting both proteins.
Oral squamous cell carcinoma (OSCC) is a common epithelial malignancy of the oral cavity. Nodal and Cripto-1 (CR-1) are important developmental morphogens expressed in several adult cancers and are associated with disease progression. Whether Nodal and CR-1 are simultaneously expressed in the same tumor and how this affects cancer biology are unclear. We investigate the expression and potential role of both Nodal and CR-1 in human OSCC. Immunohistochemistry results show that Nodal and CR-1 are both expressed in the same human OSCC sample and that intensity of Nodal staining is correlated with advanced-stage disease. However, this was not observed with CR-1 staining. Western blot analysis of lysates from two human OSCC line experiments shows expression of CR-1 and Nodal, and their respective signaling molecules, Src and ERK1/2. Treatment of SCC25 and SCC15 cells with both Nodal and CR-1 inhibitors simultaneously resulted in reduced cell viability and reduced levels of P-Src and P-ERK1/2. Further investigation showed that the combination treatment with both Nodal and CR-1 inhibitors was capable of reducing invasiveness of SCC25 cells. Our results show a possible role for Nodal/CR-1 function during progression of human OSCC and that targeting both proteins simultaneously may have therapeutic potential.
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