Preliminary Study On The Role Of Nlp In Tumor Microenvironment

As a centrosome protein, Nlp was recently found to be oncogenic. The known mechanisms for its oncogenic properties were centered on promoting cellular proliferation, anti-apoptosis and inducing genomic instability. Tumor microenvironment is considered a prevailing mechanism in the development of various tumors, especially in tumor invasion and metastasis. In the current study, the connection of Nlp and tumor microenvironment was examined to explore the latter’ s role in Nlp oncogenic properties.We first detected the effect of Nlp on endothelial cells and macrophages, which are major cells in microenvironment. The in-vitro study showed that conditioned media from Nlp-overexpressed cells significantly increased the migration of endothelial cells and macrophages. It indicates that Nlp can alter the microenvironment of tumor. Some microenvironment related molecules were then detected changed in Nlp-overexpressed cells by transcriptome chip and the following bioinformatics analyses. The validation to these molecules by RT-PCR showed that CGA and TGM2were significantly changed in mRNA level. Western Blot showed that TGM2and VEGFa were differentially expressed in protein level. We finally examined the expression and subcellular location of some upstream molecules associated with microenvironment by Western Blot and Immunofluorescence. ERK1was found to be upregulated in Nlp-overexpressed cells.Taken together, Nlp regulates microenvironment by promoting the migration capacity of endothelial cells and macrophages. The process could be mediated by VEGFa, CGA, TGM2and their upstream molecule-ERKl, which requires further investigation.