Expression of fatty acid binding protein 4 is involved in the cell growth of oral squamous cell carcinoma

Abstract

Abstract. Fatty acid binding proteins (FABPs) are a family of small and highly conserved lipid chaperone molecules with highly varied functions. Among them, fatty acid binding protein 4 (FABP4, also known as aP2) is highly expressed by adipocytes, macrophages and dendritic cells. Although the role of FABP4 in cancer is still unclear, it has been reported to be highly expressed by human tumors such as ovarian and bladder cancers. In the present study, we investigated the expression and role of FABP4 in oral squamous cell carcinoma (SCC) and its expression in oral SCC tissues. Immunohistochemical staining revealed that FABP4 expression in the tumor tissue was much higher than that in the non-tumor area of the same specimen. In the in vitro studies, an FABP4-knockdown SCC cell line (established through FABP4-specific siRNA) showed inhibited growth, and inhibited expression and activation of mitogen-activated protein kinase (MAPK). These results indicate that expression of FABP4 plays an important role in the cell growth of oral SCC through the MAPK pathway. IntroductionOral squamous cell carcinoma (SCC) is a major neoplasm of the oral cavity with an increasing rate of incidence (1-3). The optimal therapy for early oral SCC is surgery, but the overall survival rate has exhibited only a slight change (1-3). Therefore, more effective therapies for oral SCC are needed.Fatty acid binding proteins (FABPs) are a family of small and highly conserved lipid chaperone molecules that bind long-chain fatty acids and other hydrophobic ligands. Their functions are wide ranging (4-6). Among them, fatty acid binding protein 4 (FABP4, also known as aP2) is highly expressed in adipocytes, macrophages and dendritic cells (5,7). As a result of its distribution, FABP4 is the most extensively researched FABP in endocrinology and metabolomics. FABP4 affects metabolic syndrome progression; FABP4-deficient mice were found to have reduced hyperinsulinemia and insulin resistance in obesity (7,8) and showed protection from atherosclerosis (9).However, little is known concerning the role of FABP4 in cancer, including oral SCC. Recently, Nieman et al (10) reported that adipocytes promote ovarian cancer metastasis and tumor cell growth by providing energy mediated by FABP4. Therefore, increased FABP4 expression may affect the growth of various tumor types. Our research group also reported that molecules controlled by peroxisome proliferator-activated receptor γ (PPARγ) play key roles in SCC growth (11-15). As FABP4 is known to mediate transcription with PPARγ (4,16), we hypothesized that FABP4 may regulate SCC growth. Therefore, in the present study, we investigated FABP4 expression and its effects on SCC of the tongue. Materials and methodsTissue samples. All clinical studies were approved by the Ethics Committee of Osaka University Dental Hospital, Osaka. Twenty-seven SCC specimens from resected tongue tissue were obtained at the Osaka University Dental Hospital during 1986-2008 after patient informed consent (Table I). Patients received no pre...

Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer (NSCLC)

“…Several studies have demonstrated the association between FABP4 expression and poor prognosis in several tumors [38-40], which were consistent with our current findings. However, the role of FABP3 in tumor is controversial: FABP3 can act as either a tumor suppressor or an oncogene depending on tumor types.…”

“…It functions in both glucose and lipid metabolism [29, 30], and is involved in signal transduction [31], as well as in cell proliferation and apoptotic processes [32]. Its involvement in tumorigenesis has been investigated in bladder cancer [12], breast cancer [33, 34], ovarian cancer [35, 36], and oral squamous cell cancer [37]. However, there have been few studies of FABPs in NSCLC patients.…”

Metabolic functions of FABPs—mechanisms and therapeutic implications

“…40 Other investigators have described potential roles for FABP4 in endothelial cell growth and blood vessel branching, 108–113 and FABP4 has also been implicated in cancer cell growth and metastasis. 114–116 The mechanisms that underly these effects are not fully understood and indeed might be pleiotropic; for example, whether the protection from asthma in Fabp4 − / − mice 40 is due to changes in immune responses, alterations in bronchoepithelial cells, other stromal cells or both, is unclear. Finally, conditions of ectopic lipid accumulation in tissues, especially in the presence of inflammatory and stress responses, might produce a permissive milieu that activates aberrant FABP expression in cells such as hepatocytes, or trigger expression from resident immune cells such as Kupffer cells.…”

Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer

“…However, it has been shown that FAS is overexpressed in numerous human cancers, including bladder cancer, and its expression level is positively correlated with tumor progression [67]. Similar to FAS, fatty acid binding proteins (FABPs) are involved in lipid metabolism and facilitate the transfer of lipids, including lipid droplets for storage, across various cellular membranes and compartments [68–70]. Adipocyte-type FABP (A-FABP), also known as adipocyte protein 2 (aP2) and fatty acid binding protein 4 (FABP4), binds to long chain fatty acids and PPAR γ agonists [69].…”