Association of latent membrane protein 1 and matrix metalloproteinase 9 with metastasis in nasopharyngeal carcinoma

Abstract

BACKGROUND Nasopharyngeal carcinoma (NPC) is a highly metastatic carcinoma whose consistent association with Epstein–Barr virus (EBV) has been established. Latent membrane protein 1 (LMP1), an EBV membrane protein expressed in latent infection, is considered to be the EBV oncoprotein. Matrix metalloproteinase 9 (MMP9), one of the MMP families, degrades Type IV collagen, a major component of extracellular matrix and is believed to be crucial for cancer invasion and metastasis. Although MMP9 is reported to be expressed in a variety of cancers, no reports concerning NPC have been published to date to the authors' knowledge. Recently, the authors have shown that LMP1 induces MMP9 in vitro cell line, which suggests the possibility of a mechanism in which LMP1 of EBV contributes to the metastasis and tumorigenesis of NPC by the induction of MMP9. METHODS The expressions of LMP1 and MMP9 were immunohistochemically examined in 38 NPC sections, and the relation of these proteins were statistically analyzed. The authors also analyzed the associations of these proteins with clinical features. RESULTS Both LMP1 and MMP9 proteins were predominantly immunolocalized in cancer nests. The expression of MMP9 showed a significant positive correlation with the expression of LMP1 (r = 0.75; P < 0.0001). Also, the expression of MMP9 correlated with lymph node metastasis (P = 0.0004). CONCLUSIONS The results suggest that the induction of MMP9 by LMP1 contributes to the metastatic potential of NPC. Cancer 2000;89:715–23. © 2000 American Cancer Society.

Metaanalysis of the significance of matrix metalloproteinases for lymph node disease in patients with head and neck squamous cell carcinoma

“…Due to lack of data, however, nine articles had to be excluded from the current metaanalysis. The remaining 5 publications with a total of 238 patients 7,9,[17][18][19] demonstrated MMP-9 expression in 150 tissue specimens. The common odds ratio is summarized in Table 2.…”

“…cN status and pN status were considered in two publications, 7,17 whereas one publication considered only pN status, 18 and two other publications 9,19 did not provide any information about lymph node status. None of the studies mentioned compared levels of MMP-expression with cN status or pN status.…”

“…None of the studies mentioned compared levels of MMP-expression with cN status or pN status. Two studies 18,19 compared the level of MMP expression with tumor status. A heterogeneity check led to a P value of 1.0, which confirmed homogeneity.…”

“…Sawatsubashi et al, 8 Krecicki et al, 11 and Repassy et al 13 differentiated between "immune reaction" and "no immune reaction." The original articles published by Horikawa et al 18 and Kurahara et al 7 did not provide exact definitions of "expression" and "no expression." Kurahara et al 7 divided the specimens according to their staining into four groups.…”

Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma

“…However, no direct evidence that the R-S cells infected by EBV express TIMP-1 in vitro has been demonstrated. Recently, it has been shown that EBVencoded latent membrane protein-1 (LMP-1) can upregulate MMP-1, 36 or MMP-9 by activating the NF-kB signaling pathway, 37,38 but downregulate reversion-inducing-cysteine-rich protein with Kazal TIMP-1 expression in diffuse large B-cell lymphoma J-W Choi et al motifs (RECK) via the activation of ERK/Sp1 signaling pathway. 39 The RECK encodes a GPI-anchored glycoprotein harboring three protease inhibitor-like domains.…”