Prox1 and FOXC2 Act as Regulators of Lymphangiogenesis and Angiogenesis in Oral Squamous Cell CarcinomaReport as inadecuate




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Prospero homeobox 1 Prox1 and forkhead box FOX C2 regulate angiogenesis and-or lymphangiogenesis. However, the detailed role and function of Prox1 and FOXC2 in cancer remains controversial. In the present study, we examined the expression of Prox1 and FOXC2 proteins in specimens from 163 cases with oral squamous cell carcinoma OSCC. Furthermore, the role of Prox1 and FOXC2 in cancer cell growth and invasion was evaluated in cultured OSCC cells. Prox1 expression was significantly associated with local progression of the tumor P = 0.0023, clinical stage P<0.0001, lymphovessel density LVD P<0.0001, nodal metastasis P<0.0001, and worse prognosis P<0.0001. Immunoreactivity of FOXC2 was strongly correlated with microvessel density MVD P<0.0001 and poor prognosis P = 0.0076. In vitro analysis demonstrated that Prox1 regulates cell growth, proliferation, invasion, and lymphangiogenesis by activating vascular endothelial growth factor VEGF-C expression. Furthermore, FOXC2 enhanced the expression level of Prox1 and promoted angiogenesis by enhancement of VEGF-A expression. Our results suggested that Prox1 and FOXC2 play key roles in OSCC progression and that further studies focusing on these proteins may yield useful insights for diagnosis and therapy of OSCC.



Author: Tomonori Sasahira, Nobuhiro Ueda, Kazuhiko Yamamoto, Miyako Kurihara, Sayako Matsushima, Ujjal K. Bhawal, Tadaaki Kirita, Hiroki

Source: http://plos.srce.hr/



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