Skip to main content
Top
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

The fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of melanoma cells

Authors: Ana Slipicevic, Kjersti Jørgensen, Martina Skrede, Anne Katrine Ree Rosnes, Gunhild Trøen, Ben Davidson, Vivi Ann Flørenes

Published in: BMC Cancer | Issue 1/2008

Login to get access

Abstract

Background

The molecular mechanisms underlying melanoma tumor development and progression are still not completely understood. One of the new candidates that emerged from a recent gene expression profiling study is fatty acid-binding protein 7 (FABP7), involved in lipid metabolism, gene regulation, cell growth and differentiation.

Methods

We studied the functional role of FABP7 in human melanoma cell lines and using immunohistochemistry analyzed its expression pattern and clinical role in 11 nevi, 149 primary melanomas and 68 metastases.

Results

FABP7 mRNA and protein level is down-regulated following treatment of melanoma cell lines with a PKC activator (PMA) or MEK1 inhibitor (PD98059). Down-regulation of FABP7 using siRNA decreased cell proliferation and invasion but did not affect apoptosis. In clinical specimens, FABP7 was expressed in 91% of nevi, 71% of primary melanomas and 70% of metastases, with a cytoplasmic and/or nuclear localization. FABP7 expression was associated with tumor thickness in superficial spreading melanoma (P = 0.021). In addition, we observed a trend for an association between FABP7 expression and Ki-67 score (P = 0.070) and shorter relapse-free survival (P = 0.069) in this group of patients.

Conclusion

Our data suggest that FABP7 can be regulated by PKC and the MAPK/ERK1/2 pathway through independent mechanisms in melanoma cell lines. Furthermore, FABP7 is involved in cell proliferation and invasion in vitro, and may be associated with tumor progression in melanoma.
Appendix
Available only for authorised users
Literature
2.
go back to reference Jorgensen K, Skrede M, Cruciani V, Mikalsen SO, Slipicevic A, Florenes VA: Phorbol ester phorbol-12-myristate-13-acetate promotes anchorage-independent growth and survival of melanomas through MEK-independent activation of ERK1/2. Biochem Biophys Res Commun. 2005, 329: 266-274. 10.1016/j.bbrc.2005.01.143.CrossRefPubMed Jorgensen K, Skrede M, Cruciani V, Mikalsen SO, Slipicevic A, Florenes VA: Phorbol ester phorbol-12-myristate-13-acetate promotes anchorage-independent growth and survival of melanomas through MEK-independent activation of ERK1/2. Biochem Biophys Res Commun. 2005, 329: 266-274. 10.1016/j.bbrc.2005.01.143.CrossRefPubMed
3.
go back to reference Schnutgen F, Borchers T, Muller T, Spener F: Heterologous expression and characterisation of mouse brain fatty acid binding protein. Biol Chem Hoppe Seyler. 1996, 377: 211-215.CrossRefPubMed Schnutgen F, Borchers T, Muller T, Spener F: Heterologous expression and characterisation of mouse brain fatty acid binding protein. Biol Chem Hoppe Seyler. 1996, 377: 211-215.CrossRefPubMed
4.
go back to reference Shimizu F, Watanabe TK, Shinomiya H, Nakamura Y, Fujiwara T: Isolation and expression of a cDNA for human brain fatty acid-binding protein (B-FABP). Biochim Biophys Acta. 1997, 1354: 24-28.CrossRefPubMed Shimizu F, Watanabe TK, Shinomiya H, Nakamura Y, Fujiwara T: Isolation and expression of a cDNA for human brain fatty acid-binding protein (B-FABP). Biochim Biophys Acta. 1997, 1354: 24-28.CrossRefPubMed
5.
go back to reference Haunerland NH, Spener F: Fatty acid-binding proteins–insights from genetic manipulations. Prog Lipid Res. 2004, 43: 328-349. 10.1016/j.plipres.2004.05.001.CrossRefPubMed Haunerland NH, Spener F: Fatty acid-binding proteins–insights from genetic manipulations. Prog Lipid Res. 2004, 43: 328-349. 10.1016/j.plipres.2004.05.001.CrossRefPubMed
6.
go back to reference Glatz JF, Storch J: Unravelling the significance of cellular fatty acid-binding proteins. Curr Opin Lipidol. 2001, 12: 267-274. 10.1097/00041433-200106000-00005.CrossRefPubMed Glatz JF, Storch J: Unravelling the significance of cellular fatty acid-binding proteins. Curr Opin Lipidol. 2001, 12: 267-274. 10.1097/00041433-200106000-00005.CrossRefPubMed
7.
go back to reference Adamson J, Morgan EA, Beesley C, Mei Y, Foster CS, Fujii H, Rudland PS, Smith PH, Ke Y: High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity. Oncogene. 2003, 22: 2739-2749. 10.1038/sj.onc.1206341.CrossRefPubMed Adamson J, Morgan EA, Beesley C, Mei Y, Foster CS, Fujii H, Rudland PS, Smith PH, Ke Y: High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity. Oncogene. 2003, 22: 2739-2749. 10.1038/sj.onc.1206341.CrossRefPubMed
8.
go back to reference Lawrie LC, Dundas SR, Curran S, Murray GI: Liver fatty acid binding protein expression in colorectal neoplasia. Br J Cancer. 2004, 90: 1955-1960. 10.1038/sj.bjc.6601828.CrossRefPubMedPubMedCentral Lawrie LC, Dundas SR, Curran S, Murray GI: Liver fatty acid binding protein expression in colorectal neoplasia. Br J Cancer. 2004, 90: 1955-1960. 10.1038/sj.bjc.6601828.CrossRefPubMedPubMedCentral
9.
go back to reference Feng L, Hatten ME, Heintz N: Brain lipid-binding protein (BLBP): a novel signaling system in the developing mammalian CNS. Neuron. 1994, 12: 895-908. 10.1016/0896-6273(94)90341-7.CrossRefPubMed Feng L, Hatten ME, Heintz N: Brain lipid-binding protein (BLBP): a novel signaling system in the developing mammalian CNS. Neuron. 1994, 12: 895-908. 10.1016/0896-6273(94)90341-7.CrossRefPubMed
10.
go back to reference Kaloshi G, Mokhtari K, Carpentier C, Taillibert S, Lejeune J, Marie Y, Delattre JY, Godbout R, Sanson M: FABP7 expression in glioblastomas: relation to prognosis, invasion and EGFR status. J Neurooncol. 2007, 84: 245-248. 10.1007/s11060-007-9377-4.CrossRefPubMed Kaloshi G, Mokhtari K, Carpentier C, Taillibert S, Lejeune J, Marie Y, Delattre JY, Godbout R, Sanson M: FABP7 expression in glioblastomas: relation to prognosis, invasion and EGFR status. J Neurooncol. 2007, 84: 245-248. 10.1007/s11060-007-9377-4.CrossRefPubMed
11.
go back to reference de Wit NJ, Rijntjes J, Diepstra JH, van Kuppevelt TH, Weidle UH, Ruiter DJ, van Muijen GN: Analysis of differential gene expression in human melanocytic tumour lesions by custom made oligonucleotide arrays. Br J Cancer. 2005, 92: 2249-2261. 10.1038/sj.bjc.6602612.CrossRefPubMedPubMedCentral de Wit NJ, Rijntjes J, Diepstra JH, van Kuppevelt TH, Weidle UH, Ruiter DJ, van Muijen GN: Analysis of differential gene expression in human melanocytic tumour lesions by custom made oligonucleotide arrays. Br J Cancer. 2005, 92: 2249-2261. 10.1038/sj.bjc.6602612.CrossRefPubMedPubMedCentral
12.
go back to reference Goto Y, Matsuzaki Y, Kurihara S, Shimizu A, Okada T, Yamamoto K, Murata H, Takata M, Aburatani H, Hoon DS, et al: A new melanoma antigen fatty acid-binding protein 7, involved in proliferation and invasion, is a potential target for immunotherapy and molecular target therapy. Cancer Res. 2006, 66: 4443-4449. 10.1158/0008-5472.CAN-05-2505.CrossRefPubMed Goto Y, Matsuzaki Y, Kurihara S, Shimizu A, Okada T, Yamamoto K, Murata H, Takata M, Aburatani H, Hoon DS, et al: A new melanoma antigen fatty acid-binding protein 7, involved in proliferation and invasion, is a potential target for immunotherapy and molecular target therapy. Cancer Res. 2006, 66: 4443-4449. 10.1158/0008-5472.CAN-05-2505.CrossRefPubMed
13.
go back to reference M-Yu Hau: Melanoma: The Wister Melanoma (WM) Cell Lines. Human Cell Culture. Edited by: Masters JR, Palsson B. 1998, 1: 259-274. M-Yu Hau: Melanoma: The Wister Melanoma (WM) Cell Lines. Human Cell Culture. Edited by: Masters JR, Palsson B. 1998, 1: 259-274.
14.
go back to reference Ishikawa M, Dennis JW, Man S, Kerbel RS: Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice. Cancer Res. 1988, 48: 665-670.PubMed Ishikawa M, Dennis JW, Man S, Kerbel RS: Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice. Cancer Res. 1988, 48: 665-670.PubMed
15.
go back to reference Fodstad O, Kjonniksen I, Aamdal S, Nesland JM, Boyd MR, Pihl A: Extrapulmonary, tissue-specific metastasis formation in nude mice injected with FEMX-I human melanoma cells. Cancer Res. 1988, 48: 4382-4388.PubMed Fodstad O, Kjonniksen I, Aamdal S, Nesland JM, Boyd MR, Pihl A: Extrapulmonary, tissue-specific metastasis formation in nude mice injected with FEMX-I human melanoma cells. Cancer Res. 1988, 48: 4382-4388.PubMed
16.
go back to reference Kobayashi H, Man S, Graham CH, Kapitain SJ, Teicher BA, Kerbel RS: Acquired multicellular-mediated resistance to alkylating agents in cancer. Proc Natl Acad Sci USA. 1993, 90: 3294-3298. 10.1073/pnas.90.8.3294.CrossRefPubMedPubMedCentral Kobayashi H, Man S, Graham CH, Kapitain SJ, Teicher BA, Kerbel RS: Acquired multicellular-mediated resistance to alkylating agents in cancer. Proc Natl Acad Sci USA. 1993, 90: 3294-3298. 10.1073/pnas.90.8.3294.CrossRefPubMedPubMedCentral
17.
go back to reference Dulic V, Lees E, Reed SI: Association of human cyclin E with a periodic G1-S phase protein kinase. Science. 1992, 257: 1958-1961. 10.1126/science.1329201.CrossRefPubMed Dulic V, Lees E, Reed SI: Association of human cyclin E with a periodic G1-S phase protein kinase. Science. 1992, 257: 1958-1961. 10.1126/science.1329201.CrossRefPubMed
18.
go back to reference Costea DE, Loro LL, Dimba EA, Vintermyr OK, Johannessen AC: Crucial effects of fibroblasts and keratinocyte growth factor on morphogenesis of reconstituted human oral epithelium. J Invest Dermatol. 2003, 121: 1479-1486. 10.1111/j.1523-1747.2003.12616.x.CrossRefPubMed Costea DE, Loro LL, Dimba EA, Vintermyr OK, Johannessen AC: Crucial effects of fibroblasts and keratinocyte growth factor on morphogenesis of reconstituted human oral epithelium. J Invest Dermatol. 2003, 121: 1479-1486. 10.1111/j.1523-1747.2003.12616.x.CrossRefPubMed
19.
go back to reference Florenes VA, Maelandsmo GM, Faye R, Nesland JM, Holm R: Cyclin A expression in superficial spreading malignant melanomas correlates with clinical outcome. J Pathol. 2001, 195: 530-536. 10.1002/path.1007.CrossRefPubMed Florenes VA, Maelandsmo GM, Faye R, Nesland JM, Holm R: Cyclin A expression in superficial spreading malignant melanomas correlates with clinical outcome. J Pathol. 2001, 195: 530-536. 10.1002/path.1007.CrossRefPubMed
20.
go back to reference Florenes VA, Faye RS, Maelandsmo GM, Nesland JM, Holm R: Levels of cyclin D1 and D3 in malignant melanoma: deregulated cyclin D3 expression is associated with poor clinical outcome in superficial melanoma. Clin Cancer Res. 2000, 6: 3614-3620.PubMed Florenes VA, Faye RS, Maelandsmo GM, Nesland JM, Holm R: Levels of cyclin D1 and D3 in malignant melanoma: deregulated cyclin D3 expression is associated with poor clinical outcome in superficial melanoma. Clin Cancer Res. 2000, 6: 3614-3620.PubMed
21.
go back to reference Florenes VA, Maelandsmo GM, Kerbel RS, Slingerland JM, Nesland JM, Holm R: Protein expression of the cell-cycle inhibitor p27Kip1 in malignant melanoma: inverse correlation with disease-free survival. Am J Pathol. 1998, 153: 305-312.CrossRefPubMedPubMedCentral Florenes VA, Maelandsmo GM, Kerbel RS, Slingerland JM, Nesland JM, Holm R: Protein expression of the cell-cycle inhibitor p27Kip1 in malignant melanoma: inverse correlation with disease-free survival. Am J Pathol. 1998, 153: 305-312.CrossRefPubMedPubMedCentral
22.
go back to reference Jorgensen K, Holm R, Maelandsmo GM, Florenes VA: Expression of activated extracellular signal-regulated kinases 1/2 in malignant melanomas: relationship with clinical outcome. Clin Cancer Res. 2003, 9: 5325-5331.PubMed Jorgensen K, Holm R, Maelandsmo GM, Florenes VA: Expression of activated extracellular signal-regulated kinases 1/2 in malignant melanomas: relationship with clinical outcome. Clin Cancer Res. 2003, 9: 5325-5331.PubMed
23.
go back to reference Mauro A, Ciccarelli C, De CP, Scoglio A, Bouche M, Molinaro M, Aquino A, Zani BM: PKCalpha-mediated ERK, JNK and p38 activation regulates the myogenic program in human rhabdomyosarcoma cells. J Cell Sci. 2002, 115: 3587-3599. 10.1242/jcs.00037.CrossRefPubMed Mauro A, Ciccarelli C, De CP, Scoglio A, Bouche M, Molinaro M, Aquino A, Zani BM: PKCalpha-mediated ERK, JNK and p38 activation regulates the myogenic program in human rhabdomyosarcoma cells. J Cell Sci. 2002, 115: 3587-3599. 10.1242/jcs.00037.CrossRefPubMed
24.
go back to reference Park MJ, Park IC, Lee HC, Woo SH, Lee JY, Hong YJ, Rhee CH, Lee YS, Lee SH, Shim BS, et al: Protein kinase C-alpha activation by phorbol ester induces secretion of gelatinase B/MMP-9 through ERK 1/2 pathway in capillary endothelial cells. Int J Oncol. 2003, 22: 137-143.PubMed Park MJ, Park IC, Lee HC, Woo SH, Lee JY, Hong YJ, Rhee CH, Lee YS, Lee SH, Shim BS, et al: Protein kinase C-alpha activation by phorbol ester induces secretion of gelatinase B/MMP-9 through ERK 1/2 pathway in capillary endothelial cells. Int J Oncol. 2003, 22: 137-143.PubMed
26.
go back to reference Blanquart C, Mansouri R, Paumelle R, Fruchart JC, Staels B, Glineur C: The protein kinase C signaling pathway regulates a molecular switch between transactivation and transrepression activity of the peroxisome proliferator-activated receptor alpha. Mol Endocrinol. 2004, 18: 1906-1918. 10.1210/me.2003-0327.CrossRefPubMed Blanquart C, Mansouri R, Paumelle R, Fruchart JC, Staels B, Glineur C: The protein kinase C signaling pathway regulates a molecular switch between transactivation and transrepression activity of the peroxisome proliferator-activated receptor alpha. Mol Endocrinol. 2004, 18: 1906-1918. 10.1210/me.2003-0327.CrossRefPubMed
27.
go back to reference Delmotte MH, Tahayato A, Formstecher P, Lefebvre P: Serine 157, a retinoic acid receptor alpha residue phosphorylated by protein kinase C in vitro, is involved in RXR. RARalpha heterodimerization and transcriptional activity. J Biol Chem. 1999, 274: 38225-38231. 10.1074/jbc.274.53.38225.CrossRefPubMed Delmotte MH, Tahayato A, Formstecher P, Lefebvre P: Serine 157, a retinoic acid receptor alpha residue phosphorylated by protein kinase C in vitro, is involved in RXR. RARalpha heterodimerization and transcriptional activity. J Biol Chem. 1999, 274: 38225-38231. 10.1074/jbc.274.53.38225.CrossRefPubMed
28.
go back to reference Issemann I, Prince R, Tugwood J, Green S: A role for fatty acids and liver fatty acid binding protein in peroxisome proliferation?. Biochem Soc Trans. 1992, 20: 824-827.CrossRefPubMed Issemann I, Prince R, Tugwood J, Green S: A role for fatty acids and liver fatty acid binding protein in peroxisome proliferation?. Biochem Soc Trans. 1992, 20: 824-827.CrossRefPubMed
29.
go back to reference Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM: mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994, 8: 1224-1234. 10.1101/gad.8.10.1224.CrossRefPubMed Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM: mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 1994, 8: 1224-1234. 10.1101/gad.8.10.1224.CrossRefPubMed
30.
go back to reference Mita R, Coles JE, Glubrecht DD, Sung R, Sun X, Godbout R: B-FABP-expressing radial glial cells: the malignant glioma cell of origin?. Neoplasia. 2007, 9: 734-744. 10.1593/neo.07439.CrossRefPubMedPubMedCentral Mita R, Coles JE, Glubrecht DD, Sung R, Sun X, Godbout R: B-FABP-expressing radial glial cells: the malignant glioma cell of origin?. Neoplasia. 2007, 9: 734-744. 10.1593/neo.07439.CrossRefPubMedPubMedCentral
31.
go back to reference Das R, Hammamieh R, Neill R, Melhem M, Jett M: Expression pattern of fatty acid-binding proteins in human normal and cancer prostate cells and tissues. Clin Cancer Res. 2001, 7: 1706-1715.PubMed Das R, Hammamieh R, Neill R, Melhem M, Jett M: Expression pattern of fatty acid-binding proteins in human normal and cancer prostate cells and tissues. Clin Cancer Res. 2001, 7: 1706-1715.PubMed
32.
go back to reference Hammamieh R, Chakraborty N, Barmada M, Das R, Jett M: Expression patterns of fatty acid binding proteins in breast cancer cells. J Exp Ther Oncol. 2005, 5: 133-143.PubMed Hammamieh R, Chakraborty N, Barmada M, Das R, Jett M: Expression patterns of fatty acid binding proteins in breast cancer cells. J Exp Ther Oncol. 2005, 5: 133-143.PubMed
33.
go back to reference Ohlsson G, Moreira JM, Gromov P, Sauter G, Celis JE: Loss of expression of the adipocyte-type fatty acid-binding protein (A-FABP) is associated with progression of human urothelial carcinomas. Mol Cell Proteomics. 2005, 4: 570-581. 10.1074/mcp.M500017-MCP200.CrossRefPubMed Ohlsson G, Moreira JM, Gromov P, Sauter G, Celis JE: Loss of expression of the adipocyte-type fatty acid-binding protein (A-FABP) is associated with progression of human urothelial carcinomas. Mol Cell Proteomics. 2005, 4: 570-581. 10.1074/mcp.M500017-MCP200.CrossRefPubMed
34.
go back to reference Liang Y, Bollen AW, Aldape KD, Gupta N: Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma. BMC Cancer. 2006, 6: 97-10.1186/1471-2407-6-97.CrossRefPubMedPubMedCentral Liang Y, Bollen AW, Aldape KD, Gupta N: Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma. BMC Cancer. 2006, 6: 97-10.1186/1471-2407-6-97.CrossRefPubMedPubMedCentral
35.
go back to reference Godbout R, Bisgrove DA, Shkolny D, Day RS: Correlation of B-FABP and GFAP expression in malignant glioma. Oncogene. 1998, 16: 1955-1962. 10.1038/sj.onc.1201740.CrossRefPubMed Godbout R, Bisgrove DA, Shkolny D, Day RS: Correlation of B-FABP and GFAP expression in malignant glioma. Oncogene. 1998, 16: 1955-1962. 10.1038/sj.onc.1201740.CrossRefPubMed
Metadata
Title
The fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of melanoma cells
Authors
Ana Slipicevic
Kjersti Jørgensen
Martina Skrede
Anne Katrine Ree Rosnes
Gunhild Trøen
Ben Davidson
Vivi Ann Flørenes
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-276

Other articles of this Issue 1/2008

BMC Cancer 1/2008 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine