Journal
CLINICAL CANCER RESEARCH
Volume 14, Issue 21, Pages 6979-6987Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-08-0090
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Funding
- National Science Council of Taiwan [NSC94-2314-B-182A-188, NSC-94-2314-B-182A-162, NSC94-2745-B-182-003-URD, NSC95-2320-B-182-049-MY2, NSC96-2314-B-182A-109-MY3]
- Chang Gung University
- Chang Gung Memorial Hospital [CMRPG360211, CTRP1001, CMRP140041]
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Purpose: We herein examine whether macrophage inflammatory protein-3 alpha (MIP-3 alpha) is a biomarker for nasopharyngeal carcinoma (NPC) and whether it is involved in modulating NPC cell functions. Experimental Design: The study population comprises 275 NPC patients and 250 controls. MIP-3 alpha levels in tissues and sera were examined by immunohistochemistry and ELISA, respectively. E8V DNA load and EBV viral capsid antigen IgA were measured by quantitative real-time PCR and immunofluorescence assay, respectively. Effects of MIP-3 alpha on NPC cell motility were investigated by Transwell migration/invasion assays and RNA interference. Results: MIP-3 alpha was overexpressed in NPC tumor cells. Serum MIP-3 alpha levels were significantly higher in untreated patients, recurrent patients and patients with distant metastases versus non-NPC controls, patients with complete remission, and long-term disease-free patients. In the prospective cohort, serum MIP-3 alpha levels were significantly higher in untreated NPC patients with advanced tumor-node-metastasis stage versus early stage and also correlated with EBV DNA load. Measurement of MIP-3 alpha, EBV DNA, and viral capsid antigen IgA levels in serial serum/plasma samples from treated patients at 6-month intervals revealed a high association between MIP-3 alpha level, E8V DNA load, and disease status. Among 155 consecutive NPC patients, subjects with pretreated MIP-3 alpha serum levels over 65 pg/mL had worse prognoses for overall survival and distant metastasis-free survival in univariate and multivariate analysis. Additionally, cell functional assays showed that MIP-3 alpha contributed to migration and invasion of NPC cells, which could be effectively inhibited by MIP-3 alpha knockdown. Conclusions: MIP-3 alpha may be a novel biomarker and prognosticator for NPC and is involved in migration and invasion of NPC cells.
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