Abstract
Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial-mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients.
Highlights
Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China and Southeast Asia [1, 2]
Serglycin expression is elevated in NPC cells with higher metastasis potential We have previously isolated and established cellular clones having different metastatic abilities from the parental NPC cell line, CNE-2 [40]
Considering the potential differences between in vivo and in vitro conditions, xenograft tumors from these 4 cell lines were collected for gene expression profiling
Summary
Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China and Southeast Asia [1, 2]. NPC has the highest metastasis rate among head and neck cancers [3–5], with the majority of the patients having metastases to regional. Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/). The molecular mechanisms underlying NPC metastasis are poorly understood. Serglycin is a proteoglycan consisting of a core protein to which negatively charged glycoaminoglycan (GAG) chains of either chondroitin sulfate or heparin are attached [7, 8]. The functions of serglycin in various cells depend on the type and size of the GAG chains decorating the core protein [8, 10–19]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
