Increased Expression of Macrophage Migration Inhibitory Factor and DJ-1 contribute to Cell Invasion and Metastasis of Nasopharyngeal Carcinoma

Abstract

Background and aim: Both macrophage migration inhibitory factor (MIF) and DJ-1 protein have been shown to relate with cell invasion and metastasis in tumors. However, the role of DJ-1 in invasion and metastasis of nasopharyngeal carcinoma (NPC) and its relation to MIF expression in NPC are not fully understood. The aim of present study is to determine whether or not MIF and DJ-1 are correlated with tumor invasion and influence a worse outcome in NPC, as well as its related mechanism.Methods: 125 cases of NPC and 45 normal tissues of nasopharynx were collected. The expression of MIF and DJ-1 in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. The association of MIF and DJ-1 with cell invasion and migration in NPC cell line were evaluated by small interfering RNA (siRNA) transfection, invasion assay and Western blotting.Results: MIF and DJ-1 staining was diffused and strong in tumor cells, whereas they were generally weaker and less common in normal lining epithelia of nasopharynx. High MIF expression in tumor cells (71.2%, 89/125 cases) were significantly associated with advanced clinical stage, lymph node metastasis, and worse prognosis of NPC patients. High expression of DJ-1 (75.2%, 94/125 cases) were closely correlated to lymph node metastasis and MIF high-expression. Only MIF high expression (P = 0.010) and lymph node metastasis (P = 0.004) emerged as strong independent prognostic factors for overall survival of NPC patients. In vitro, down-regulated expression of DJ-1 in NPC cell lines by siRNA was observed to reduce cell migration and invasion potential, however, exogenous MIF promoted cells invasion.Conclusions: The data provided evidence that increased expression of MIF and DJ-1 induced cell invasion and metastasis of NPC, supporting the idea that MIF and DJ-1 may play important roles as regulators in the progression of NPC.

Chronic Macrophage Migration Inhibitory Factor Exposure Induces Mesenchymal Epithelial Transition and Promotes Gastric and Colon Cancers

“…These data are supported by another study that shows higher MIF expression by tumor cells from nasopharyngeal carcinoma patients correlated with advanced clinical stage of disease [45]. A few studies have suggested that MIF may be involved with tumor progression, one showing that MIF induces invasion of colon cancer cells in vitro in assays using matrigel [46].…”

Mechanistic Nanotherapeutic Approach Based on siRNA-Mediated DJ-1 Protein Suppression for Platinum-Resistant Ovarian Cancer

“…Because intracellular DJ-1 is known to regulate the process of cancer cell migration, 47, 48 we also employed the wound healing assay to assess an effect of siRNA-mediated DJ-1 knockdown alone or in combination with CDDP on the migration capacity of ovarian cancer cells. Immediately after initiating an appropriate treatment, a scratch was made in the cell monolayer and migration of cancer cells to the wound area was monitored at different time points.…”

Involvement of macrophage migration inhibitory factor in cancer and novel therapeutic targets

“…In pancreatic cancer cell lines, the overexpression of MIF was associated with an increase in cell invasiveness in vitro and in vivo, with distant metastasis to the liver, spleen, lymph nodes and intestine (32). Furthermore, the MIF-associated promotion of cell invasiveness in vitro has also been demonstrated in colorectal carcinoma, nasopharyngeal carcinoma, adenoid cystic carcinoma and oral squamous cell carcinoma (11,30,45,46). Notably, matrix metalloproteinase-9 (MMP-9) expression appears to be correlated with MIF expression, as positive immunostaining of MIF increases with that of MMP-9, and MMP-9 is associated with cell invasion in adenoid cystic carcinoma tissue (46).…”