Breast cancer is the most common form of cancer among women. Compared with other serum polypeptides, autoantibodies have many appealing features as biomarkers including sensitivity, stability, and easy detection. Anti-lipid autoantibodies are routinely used in the diagnosis of autoimmune diseases, but their potential for cancer diagnosis has not been explored. Dysregulation of cellular signaling in cancer cells would be expected to lead to irregular metabolism of many lipids, which could be sensed by the immune system and cause the production of autoantibodies. Discovery of anti-lipid antibodies could be used as biomarkers for early breast cancer diagnosis. We describe here a more sensitive and accurate method for lipid microarray detection using dual fluorescent labeling, and used it to examine global anti-lipid profiles in the MMTV-Neu transgenic breast cancer model. We conclude that, at the current technology, lipid microarray is not a preferred method for anti-lipid antibody detection in breast cancer animal models. Our result will help the future application of lipid microarrays in identifying anti-lipid autoantibodies in breast cancer and other human diseases.
Breast cancer Lipid Lipid microarray Autoantibody Transgenic mouse model
This is a preview of subscription content, log in to check access.
The authors thank Ms. Yue Zeng and Dr. Wenjuan Su for their help with mouse maintenance and blood collection. This work was supported by a concept award from the Department of Defense (DOD) Breast Cancer Research Program (W81XWH-06-1-0690) and a research grant from National Institutes of Health (GM071475).
Miller LD, Liu ET. Expression genomics in breast cancer research: microarrays at the crossroads of biology and medicine. Breast Cancer Res. 2007;9:206.CrossRefPubMedGoogle Scholar
Abramovitz M, Leyland-Jones B. A systems approach to clinical oncology: focus on breast cancer. Proteome science. 2006;4:5.CrossRefPubMedGoogle Scholar
Casiano CA, Mediavilla-Varela M, Tan EM. Tumor-associated antigen arrays for the serological diagnosis of cancer. Mol Cell Proteomics. 2006;5:1745–59.CrossRefPubMedGoogle Scholar
Wang X, Yu J, Sreekumar A, Varambally S, Shen R, Giacherio D, et al. Autoantibody signatures in prostate cancer. N Engl J Med. 2005;353:1224–35.CrossRefPubMedGoogle Scholar
Rubin MA, Zhou M, Dhanasekaran SM, Varambally S, Barrette TR, Sanda MG, et al. Alpha-methylacyl coenzyme a racemase as a tissue biomarker for prostate cancer. Jama. 2002;287:1662–70.CrossRefPubMedGoogle Scholar
Zha S, Ferdinandusse S, Denis S, Wanders RJ, Ewing CM, Luo J, et al. Alpha-methylacyl-coa racemase as an androgen-independent growth modifier in prostate cancer. Cancer Res. 2003;63:7365–76.PubMedGoogle Scholar
Tomlins SA, Rubin MA, Chinnaiyan AM. Integrative biology of prostate cancer progression. Annu Rev Pathol Mech Dis. 2006;1:274–1.CrossRefGoogle Scholar
Baron A, Migita T, Tang D, Loda M. Fatty acid synthase: a metabolic oncogene in prostate cancer? J Cell Biochem. 2004;91:47–53.CrossRefPubMedGoogle Scholar
Rossi S, Graner E, Febbo P, Weinstein L, Bhattacharya N, Onody T, et al. Fatty acid synthase expression defines distinct molecular signatures in prostate cancer. Mol Cancer Res. 2003;1:707–15.PubMedGoogle Scholar
Glunde K, Ackerstaff E, Mori N, Jacobs MA, Bhujwalla ZM. Choline phospholipid metabolism in cancer: consequences for molecular pharmaceutical interventions. Mol Pharm. 2006;3:496–506.CrossRefPubMedGoogle Scholar
Hammad LA, Wu G, Saleh MM, Klouckova I, Dobrolecki LE, Hickey RJ, et al. Elevated levels of hydroxylated phosphocholine lipids in the blood serum of breast cancer patients. Rapid Commun Mass Spectrom. 2009;23:863–76.CrossRefPubMedGoogle Scholar
Kanter JL, Narayana S, Ho PP, Catz I, Warren KG, Sobel RA, et al. Lipid microarrays identify key mediators of autoimmune brain inflammation. Nat Med. 2006;12:138–43.CrossRefPubMedGoogle Scholar
Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ. Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA. 1992;89:10578–82.CrossRefPubMedGoogle Scholar
Oresic M, Hanninen VA, Vidal-Puig A. Lipidomics: a new window to biomedical frontiers. Trends Biotechnol. 2008;26:647–52.CrossRefPubMedGoogle Scholar
Schiavo N, Lottermann AL, Costa FP, Staub HL. Antiphospholipid antibodies, thrombosis, and adenocarcinoma. Clinics. 2005;60:257–8.CrossRefPubMedGoogle Scholar
Langer F, Eifrig B, Marx G, Stork A, Hegewisch-Becker S, Hossfeld DK. Exacerbation of antiphospholipid antibody syndrome after treatment of localized cancer: a report of two cases. Ann Hematol. 2002;81:727–31.CrossRefPubMedGoogle Scholar
Ravindranath MH, Muthugounder S, Presser N, Ye X, Brosman S, Morton DL. Endogenous immune response to gangliosides in patients with confined prostate cancer. Int J Cancer. 2005;116:368–77.CrossRefPubMedGoogle Scholar
Smith KA, Gale BK, Conboy JC. Micropatterned fluid lipid bilayer arrays created using a continuous flow microspotter. Anal Chem. 2008;80:7980–7.CrossRefPubMedGoogle Scholar