A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

Boiteux, Guillaume; Lascombe, Isabelle; Roche, Emmanuelle; Plissonnier, Marie-Laure; Clairotte, Anne; Bittard, Hugues; Fauconnet, Sylvie

doi:10.1002/ijc.24112

Cited by 57 publications

(59 citation statements)

References 49 publications

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“…FABP4 expression has been reported in various types of tumors such as ovarian and bladder cancers (10,22), and FABP5 (E-FAPB) has been found in oral SCC (23,24). However, the expression and exact role of FABP4 in oral SCC have not been widely investigated In the present study, using an immunohistochemical approach, we consistently found significantly higher expression of FABP4 protein in the tumor area of tongue SCC than in the non-tumor area in the same tissue samples.…”

Section: Discussionsupporting

confidence: 68%

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

et al. 2014

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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...

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Section: Discussionsupporting

confidence: 68%

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

et al. 2014

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“…This profile is characteristic of tumour suppressor genes. This possibility was previously evoked for FABP4 for the majority of bladder cancer (27). Gene expression correlation analyses showed a moderate correlation between TAGLN and NNMT [r(Pearson) = 0.59; p<0.001], and GDP1 (GPDA) and FABP4 [r(Pearson) = 0.57; p<0.001].…”

Section: Guaa) Gapdh (G3p) Cfl1 (Cof1) Gpd1 (Gpda) a Tendency Wasmentioning

confidence: 71%

“…FABP4 expression is down-regulated in breast cancer cell lines in comparison with normal breast cell lines (29). In bladder transitional cell carcinoma, FABP4 protein and RNA have been found significantly decreased with increasing tumour stage and histological grade, and it has demonstrated a good prognostic value (27,30).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: A multicentric 2004 national PHRC study

et al. 2012

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Abstract. We used a 2D-electrophoresis (2-DE) proteomic approach to identify novel biomarkers in node-negative breast cancers. This retrospective study focused on a population of patients with ductal pN0M0 tumours. A subset of patients who developed metastases and in whose tumours were found high levels of uPA and PAI-1 (metastatic relapse, MR: n=20) were compared to another subset in whom no metastatic relapse occurred and whose tumours were found to have low levels of uPA and PAI-1 (no relapse, NR: n=21). We used a 2-DE coupled with MS approach to screen cytosol fractions using two pH-gradient scales, a broad scale (3.0-11.0) and a narrower scale focussing in on a protein rich region (5.0-8.0). This study was conducted on 41 cytosol specimens analyzed in duplicate on two platforms. The differential analysis of more than 2,000 spots in 2-DE gels, obtained on the two platforms, allowed the identification of 13 proteins which were confirmed by western blotting. Two proteins, GPDA and FABP4 were down-regulated in the MR subset whereas all the others were up-regulated. An in silico analysis revealed that GMPS (GUAA), GAPDH (G3P), CFL1 (COF1) and FTL (FRIL), the most informative genes, displayed a proliferation profile (high expression in basal-like, HER2 + and luminal B molecular subtypes). Inversely, similar to FABP4, GPD1 [GPDA] displayed a high expression in luminal A subtype, a profile characteristic of tumour suppressor genes. Despite the small size of our cohort, the 2-DE analysis gave interesting results which were confirmed by the in silico analysis showing that some of the corresponding genes had a strong prognostic impact in breast cancer, mostly because of their link with proliferation: GMPS, GAPDH, FTL and GPD1. A validation phase on a larger cohort is now needed before these biomarkers could be considered for use in clinical practice.

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“…The pathological role of FABP4 is largely different among carcinomas, as it is suppressive in bladder (17,41) and breast carcinomas (18) and stimulatory in gastric (14) and ovarian carcinomas (15). FABP4 expression was identified in almost all the tongue carcinomas examined.…”

Section: Discussionmentioning

confidence: 99%

“…The ectopic expression of FABP4 in carcinomas of the stomach (14) and ovary (15) facilitates disease progression, whereas it is downregulated in aggressive subsets of bladder and breast carcinomas (16)(17)(18). These data suggest the differential role of FABP4 in carcinomas depending on the tissue origin.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of fatty acid-binding proteins and pathological implications in the progression of tongue carcinoma

Ohyama

Kawamoto

Chiba

et al. 2013

Molecular and Clinical Oncology

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Abstract. Tongue carcinomas are common malignancies of the oral cavity. Understanding the molecular mechanisms behind the disease progression is a prerequisite for improving patient prognosis. Fatty acid-binding proteins (FABPs) are cytoplasmic lipid chaperones that affect cellular organization and energy production. Although their aberrant expression is involved in carcinoma progression, its role in the pathology of tongue carcinomas remains unclear. In the present study, the immunohistochemical expression of FABP4 and FABP5 in tongue carcinomas (n=58) and its involvement in the clinicopathological parameters were examined. Normal tongue epithelial cells expressed FABP5, an epidermal-type FABP, but not FABP4, an adipocyte-type FABP. The cytoplasmic staining of FABP5 was increased in carcinomas with advanced T-stage (P<0.05) and clinical stage (P<0.05). Ectopic expression of FABP4 was detected in almost all carcinomas, although its role in disease progression remains undetermined. Upregulation of FABP5 in the wounded skin of genetically normal mice indicated that microenvironmental tissue factors induce FABP5 expression. The results of the present study demonstrated the aberrant expression of FABP4 and FABP5 in tongue carcinomas and suggested the involvement of FABP5 in disease progression.

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A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

Cited by 57 publications

References 49 publications

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

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

Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis: A multicentric 2004 national PHRC study

Differential expression of fatty acid-binding proteins and pathological implications in the progression of tongue carcinoma

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