A New Melanoma Antigen Fatty Acid–Binding Protein 7, Involved in Proliferation and Invasion, Is a Potential Target for Immunotherapy and Molecular Target Therapy

Abstract

The identification of molecules that are preferentially expressed in melanoma cells and involved in their malignant phenotypes is important for understanding melanoma biology and the development of new diagnostic and therapeutic methods. By comparing the expression profile of a melanoma cell line with those of various normal tissues using GeneChip and by confirming the actual expression of the selected genes by reverse transcription-PCR and Northern and Western blot analyses, fatty acid-binding protein 7 (FABP7), which is frequently expressed in melanomas, was identified. Immunohistochemical examination revealed that FABP7 was expressed in 11 of 15 melanoma tissues. By down-regulating the FABP7 expression with FABP7-specific small interfering RNAs, in vitro cell proliferation and Matrigel invasion were suppressed in two of six melanoma cell lines. Overexpression of FABP7 in a FABP7-negative embryonic kidney cell line 293T by transfecting with the FABP7 cDNA resulted in enhanced cell proliferation and Matrigel invasion, indicating that FABP7 plays a role in the malignant phenotype of some melanoma cell lines. IgG antibodies specific for the phage or bacterial recombinant FABP7 protein were detected in 14 of 25 (56%) or in 8 of 31 (26%) sera from melanoma patients, respectively, but not in sera from healthy individuals, indicating that FABP7 is an immunogenic antigen in melanoma patients. These results showed that FABP7 is frequently expressed in melanoma, may be involved in cell proliferation and invasion, and may be a potential target for development of diagnostic and therapeutic methods. (Cancer Res 2006; 66(8): 4443-9)

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

“…Although FABP7 expression has not been linked with blood cancers before, up-regulation has been reported in various solid cancer types, including malignant glioma (28), melanoma (31), renal cell carcinoma (30), and aggressive triple negative breast cancer (47) and is associated with poor prognosis and also increased cell growth in vitro (48). To assess the requirement for chimeric FABP7 in DLBCL proliferation and cell-cycle progression in vitro, DLBCL cell lines were nucleofected to express three independent RNAi sequences targeting FABP7 and a nonsilencing scrambled control sequence.…”

“…Hence, any FABP7-specific chemotherapeutic treatments that do not cross the blood-brain barrier could be highly cancer-specific, making FABP7 a potentially useful therapeutic target. FABP7 is up-regulated in several solid cancer types, including melanoma (28)(29)(30)(31)47), and has previously been recognized as a novel target for a melanoma treatment (48). It is worth noting that most of these studies would not have detected differential promoter use of FABP7, so it is possible that the LTR2 element might also drive expression of this gene in other cancers.…”

Human High Molecular Weight–Melanoma-Associated Antigen: Utility for Detection of Metastatic Melanoma in Sentinel Lymph Nodes

“…RNA was quantified and assessed for purity by UV spectrophotometry and a RIBOGreen detection assay (Molecular Probes; ref. 16).…”

Aplidin synergizes with cytosine arabinoside: functional relevance of mitochondria in Aplidin-induced cytotoxicity

“…Fatty acid-binding protein 7, suggested recently in literature to be a potential new target for cancer, was downregulated 25-fold after 15 min following drug exposure as well as a-methylacyl-CoA racemase (5-fold), a mitochondrial enzyme responsible for the b-oxidation of branched fatty acids. 20 Glycoprotein synthesis was affected by downregulation of 1,4-galactosyltransferase and N-acetylgalactosaminyltransferase 8 after 15 min, and lasted up to 24 h. Transcription was affected by downregulation of SET domain containing 1A (10-fold), histone methyltransferase, primarily responsible for H3Lys9 methylation, RNA polymerase II polypeptide A (5-fold), mediator of RNA polymerase II transcription (4-fold) and ADP-ribosyltransferase 3 (10-fold) following 15 min or 1 h exposure to Aplidin. In summary, Aplidin affects energy metabolism, presumably by inhibiting the TCA cycle, and fatty acid metabolism.…”