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Metastatic potential of CNE-2 cells

ABSTRACT: Nasopharyngeal carcinoma (NPC) is known for its high metastatic potential. From genomic expression profiles comparing clones derived from the NPC cell line CNE-2, serglycin (SRGN) was identified as one of the most up-regulated genes in the high-metastasis clone. Serglycin protein was secreted by the high-metastasis clone, but not by any of the low-metastasis clones. Suppression of serglycin by shRNA diminished serglycin secretion and subsequently inhibited the migration and invasion of high-metastasis clone, and also reduced its metastasis rate in vivo. Overexpression of serglycin in low-metastasis cells resulted in an increased metastasis rate in vivo. Moreover, secreted serglycin promoted cellular motility in the wild-type low-metastasis cells. Interestingly, suppression of serglycin reduced the protein level of vimentin but did not influence the level of E-cadherin in high-metastasis clone. Proliferation was not influenced by serglycin in both high-and low-metastasis clones. Clinically, serglycin expression was significantly elevated in liver metastases from NPC relative to its expression in primary tumors. The prognostic value of serglycin was evaluated by immunohistochemical staining of tissue microarrays of NPC tissues from 263 patients, followed by multivariate analyses. A high level of serglycin expression in primary NPC was found to be an independent unfavorable indicator for distant-metastasis-free survival and disease-free survival. In summary, serglycin regulates NPC metastasis via autocrine and paracrine means without influencing proliferation, and it serves as a prognostic indicator of metastasis-free survival and disease-free survival for NPC patients. Keywords: Gene Expression experiment

ORGANISM(S): Homo sapiens

PROVIDER: GSE24154 | GEO | 2011/02/14

SECONDARY ACCESSION(S): PRJNA130039

REPOSITORIES: GEO

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Project description:Nasopharyngeal carcinoma (NPC) is known for its high metastatic potential. From genomic expression profiles comparing clones derived from the NPC cell line CNE-2, serglycin (SRGN) was identified as one of the most up-regulated genes in the high-metastasis clone. Serglycin protein was secreted by the high-metastasis clone, but not by any of the low-metastasis clones. Suppression of serglycin by shRNA diminished serglycin secretion and subsequently inhibited the migration and invasion of high-metastasis clone, and also reduced its metastasis rate in vivo. Overexpression of serglycin in low-metastasis cells resulted in an increased metastasis rate in vivo. Moreover, secreted serglycin promoted cellular motility in the wild-type low-metastasis cells. Interestingly, suppression of serglycin reduced the protein level of vimentin but did not influence the level of E-cadherin in high-metastasis clone. Proliferation was not influenced by serglycin in both high-and low-metastasis clones. Clinically, serglycin expression was significantly elevated in liver metastases from NPC relative to its expression in primary tumors. The prognostic value of serglycin was evaluated by immunohistochemical staining of tissue microarrays of NPC tissues from 263 patients, followed by multivariate analyses. A high level of serglycin expression in primary NPC was found to be an independent unfavorable indicator for distant-metastasis-free survival and disease-free survival. In summary, serglycin regulates NPC metastasis via autocrine and paracrine means without influencing proliferation, and it serves as a prognostic indicator of metastasis-free survival and disease-free survival for NPC patients. Keywords: Gene Expression experiment High-metastasis clone (S18) and low-metastasis clones (S22 and S26) together with their parental line CNE-2 were subjected for gene expression profiling to identify the genes highly expressed in high-metastasis clone. To explore the molecular mechanism(s) underlying this important biological behavior, we performed genomic expression profiling of these four cell lines from in vitro cultured cells, as well as in vivo xenograft tumors generated in nude mice by subcutaneous injection of the cells into the BALB/c (nu/nu) female mice. Briefly, 1 × 10^5 cells were subcutaneously injected into the left flank of a nude mouse, and the tumors were collected when their volume was 150-250 mm^3.

Project description:Vascular endothelial growth factor is a multifunctional cytokine playing important roles in angiogenesis, tumor progression and metastasis. Alternative splicing results in the production of several different isoforms of VEGF. We have previously generated human breast cancer cells overexpressing VEGF165 or VEGF189 isoforms (referred to as the V165 and V189 clones, respectively) and showed that VEGF189-transfected cells were less tumorigenic. In this study, we used bioluminescence imaging to analyze the metastasis capacity of breast cancer cell lines (MDA-MB-321) overexpressing VEGF isoforms in nude mice. V165, V189 and control cV clones were transfected with a luciferase plasmid to generate bioluminescent clones (the V165-B, V189-B and cV clones, respectively). These clones were then injected into the left heart ventricle of nude mice. Analysis of the location of metastases shows that V189-B cells induced fewer metastases in lung and bone than V165-B and cV-B cells. Moreover, there was a delay on metastasis appearance in mice receiving VEGF V189-B clone, consistent with increase survival in these mice. We investigated the possible mechanisms underlying these effects and found that VEGF189 increased adhesion and decreased cell invasion and survival in vitro. In the other side, transcriptomic analyses shown expression of genes, implicated in breast cancer and metastatic dissemination, in VEGF165 overexpressing cells. After in silico analyses of genes differentially expressed between V189 and V165 cells,we used Q-PCR assays to quantify mRNA levels of some gene of interest in 120 breast tumors from patients with or without metastasis and/or specially lung metastasis. We found that genes have prognostical significance and /or showed an influence on relapse-free survival. These data provide the first evidence that different VEGF isoforms have different effects on breast cancer cell line invasion and colonization. Human MDA-MB-231 breast cancer cells were used to generate stable transfected clones overexpressing VEGF165 isoform, VEGF189 isoform, or control vector (referred to as 42ctl8, 13ctl3 and PCIctl3, respectively). Analysis of the metastasis capacity of these clones in nude mice.

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Metastatic potential of CNE-2 cells

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