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Improved detection Of the MUC1 cancer antigen CA 15-3 by ALYGNSA fluorimmunoassay

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DOI: 10.4236/health.2011.38087    4,543 Downloads   9,742 Views   Citations

ABSTRACT

Breast cancer is the second leading cause of cancerrelated deaths in women worldwide; a prime cancer biomarker to aid in the diagnosis, directed treatment, clinical management, and reoccurrence of this cancer is a MUC1 peptide fragment: cancer antigen 15-3 (CA 15-3). Herein, an immuno-fluorescence assay for CA 15-3 was developed; this ALYGNSA system consists of a protein biolinker (Protein G’) adsorbed onto Poly (methyl methacrylate) (PMMA). The unique interaction of Protein G’ with PMMA, a thermo-plastic polymer has been demonstrated to improve human IgG capture antibody alignment/ orientation and result in greater assay sensitivity. Indeed a previous report (HEALTH 1 325 - 329, 2009) on the shed extracellular domain of HER-2/neu revealed a 10-fold increase in sensitivity of the ALYGSNA assay over a control ELISA assay. Results from this ALYGNSA assay study revealed that a 16-fold increase in detection (≤0.94 U/mL) of CA 15-3 was found in comparison to a commercial control ELISA kit (≤15 U/mL). In conclusion, this enhanced sensitivity of the ALYGNSA assay for CA 15-3, may provide insights into the role/function of this biomarker in normal, as well as, breast cancer and other epithelial cancers.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Chourb, S. , Mackness, B. , Farris, L. and McDonald, M. (2011) Improved detection Of the MUC1 cancer antigen CA 15-3 by ALYGNSA fluorimmunoassay. Health, 3, 524-528. doi: 10.4236/health.2011.38087.

References

[1] Jemal, A., Siegel, R., Xu, J. and Ward, E. (2010) Cancer Statics. CA Cancer Journal for Clinicians, 60, 277-300. doi:10.3322/caac.20073
[2] Moelans, C.B., de Weger, R.A., Van der Wall, E. and van Diest, P.J. (2011) Current technologies for HER2 testing in breast cancer. Critical Reviews in Oncology/Hemato- logy, Accessed May 5, 2011. doi:10.1074/mcp.R400001-MCP200
[3] Ross, J.S., Fletcher, J.A., Linette, G.P., Stec, J., Clark, E., Ayers, M., et al. (2004) Targeted therapy in breast cancer: The HER-2/neu gene and protein. Molecular & Cellular Proteomics, 3, 379-398. doi:10.1074/mcp.R400001-MCP200
[4] Bramwell, V.H.C., Doig, G.S., Tuck, A.B., Wilson, S.M., Tonkin, K.S., Tomiak, A., et al. (2009) Changes over time of extracellular domain of HER2 (ECD/HER2) serum levels have prognostic value in metastatic breast cancer. Breast Cancer Research and Treatment, 114, 503-511. doi:10.1007/s10549-008-0033-2
[5] Carney, W.P., Leitzel, K., Ali, S., Neumann, R. and Lipton, A. (2007) HER-2/neu diagnostics in breast cancer. Breast Cancer Research, 9, 207-217. doi:10.1186/bcr1664
[6] Jones, S.E. (2008) Metastatic breast cancer: The treatment challenge. Clinical Breast Cancer, 8, 224-233. doi:10.1038/nrc2761
[7] Mukhopadhyay, P., Chakraborty, S., Ponnusamy, M.P., Lakshmanan, I., Jain, M. and Batra, S. K. (2011) Mucins in the pathogenesis of breast cancer: Implications in diagnosis, prognosis and therapy. Biochimica et Biophysica Acta, 1815, 224-240.
[8] Kufe, D.W. (2009) Mucins in cancer: Function, prognosis and therapy. Nature Reviews Cancer, 9, 874-885. doi:10.1016/j.tibs.2009.10.003
[9] Senapati, S., Das, S. and Batra, S.K. (2010) Mucin-interacting proteins: From function to therapeutics. Trends in Biochemical Sciences, 35, 236-245. doi:10.1016/j.tibs.2009.10.003
[10] Duffy, M.J. (1999) CA 15-3 and related mucins as cir- culating markers in breast cancer. Annals of Clinical Biochemistry, 36, 579-586.
[11] Bafna, S., Kaur, S. and Batra, S.K. (2010) Membrane-bound mucins: The mechanistic basis for alterations in the growth and survival of cancer cells. Oncogene, 29, 2893-2904. doi:10.1038/onc.2010.87
[12] Lagow, E., DeSouza, M.M. and Carson, D.D. (1999) Mammalian reproductive tract mucins. Human Repro- duction, 15, 280-292.
[13] Agrawal, B., Gendler, S.J. and Longenecker, B.M. (1998) The biological role of mucins in cellular interactions and immune regulation: Prospects for cancer immunotherapy. Molecular Medicine Today, 4, 397-403. doi:10.1016/S1357-4310(98)01322-7
[14] Brayman, M., Thathiah, A. and Carson, D.D. (2004) MUC1: A multifunctional cell surface component of reproductive tissue epithelia. Reproductive Biology and Endocrinology, 2, 1-9. doi:10.1186/1477-7827-2-4
[15] Parry, S., Silverman, H.S., McDermott, K., Willis, A., Hollingsworth, M.A. and Harris, A. (2001) Identification of MUC1 proteolytic cleavage sites in vivo. Biochemical and Biophysical Research Communications, 283, 715- 720. doi:10.1006/bbrc.2001.4775
[16] Welsh, J.B., Sapinoso, L.M., Kern, S.G., Brown, D.A., Liu, T., Bauskin, A.R., et al. (2003) Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum. Proceedings of the National Academy of Sciences USA, 100, 3410-3415. doi:10.1073/pnas.0530278100
[17] Duffy, M.J., Duggan, C., Keane, R., Hill, A.D.K., McDermott, E., Crown, J. and O’Higgins, N. (2004) High preoperative CA 15-3 concentrations predict adverse outcome in node-negative and node-positive breast cancer: Study of 600 patients with histologically confirmed breast cancer. Clinical Chemistry, 50, 559-563. doi:10.1373/clinchem.2003.025288
[18] Tampellini, M., Berruti, A., Gerbino, A., Buniva, T., Torta, M., Gorzegno, G., et al. (1997) Relationship between CA 15-3 serum levels and disease extent in predicting overall survival of breast cancer patients with newly diagnosed metastatic disease. British Journal of Cancer, 75, 698-702. doi:10.1038/bjc.1997.124
[19] Kim, H.S., Park, Y.H., Park, M.J., Chang, M.H., Jun, H.J., Kim, K.H., et al. (2009) Clinical significance of a se- rum CA15-3 surge and the usefulness of CA15-3 kinetics in monitoring chemotherapy response in patients with metastatic breast cancer. Breast Cancer Research and Treatment, 118, 89-90. doi:10.1007/s10549-009-0377-2
[20] Clarizia, L.-J.A., Sok, D., Wei, M., Mead, J., Barry, C. and McDonald, M.J. (2009) Antibody orientation enhanced by selective polymer–protein noncovalent interactions. Analytical and Bioanalytical Chemistry, 393, 1531-1538. doi:10.1007/s00216-008-2567-x
[21] Chourb, S., Mackness, B.C., Farris, L.R. and McDonald, M.J. (2009) Enhanced immuno-detection of shed extracellular domain of HER-2/neu. Health, 1, 325-329. doi:10.4236/health.2009.14053
[22] Sok, D., Clarizia, L.-J.A., Farris, L.R. and McDonald, M.J. (2009) Novel fluoroimmunoassay for ovarian cancer biomarker CA-125. Analytical and Bioanalytical Chemistry, 393, 1521-1523. doi:10.1007/s00216-008-2569-8
[23] Mackness, B.C., Chourb, S., Farris, L.R. and McDonald, M.J. (2010) Polymer-protein-enhanced fluoroimmunoassay for prostate-specific antigen. Analytical and Bioanalytical Chemistry, 396, 681-686. doi:10.1007/s00216-009-3234-6
[24] Mackness, B.C. and McDonald, M.J. (2010) Serum- -Based ALYGNSA immunoassay for the prostate cancer biomarker, total prostate-specific antigen (tPSA). Analytical and Bioanalytical Chemistry, 397, 3151-3154. doi:10.1007/s00216-010-3827-0
[25] Chourb, S. (2010) Enhanced immuno-detection of breast cancer biomarkers: Shed extracellular domain of Her-2/ neu and CA 15-3. Master’s Thesis, University of Massachusetts Lowell, Lowell.
[26] Sturgeon, C.M., Duffy, M.J., Stenman, U.H., Lilja, H., Brünner, N., Chan, D.W., et al. (2008) National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in prostate, colorec- tal, breast and ovarian cancers. Clinical Chemistry, 54, e11-e79. doi:10.1373/clinchem.2008.105601
[27] Pichon, M.F., Brun, G.L., Hacene, K., Basuyau, J.P., Riedinger, J.M., Eche, N., Fulla, Y. and Charlier-Bret, N., (2009) Comparison of fifteen immunoassays for the measurement of serum MUC-1/CA 15-3 in breast cancer patients. Clinical Chemistry and Laboratory Medicine, 47, 985-992. doi:10.1515/CCLM.2009.213
[28] Bon, G.G., Kenemans, P., Dekker, J.J., Hompes, P.G., Ver- straeten, R.A., van Kamp, G.J. and Schoemaker, J. (1999) Fluctuations in CA 125 and CA 15–3 serum concentra- tions during spontaneous ovulatory cycles. Human Reproduction, 14, 566-570. doi:10.1093/humrep/14.2.566
[29] Jonckheere, N. and Van Seuningen, I. (2010) The membranebound mucins: From cell signaling to transcriptional regulation and expression in epithelial cancers. Biochimie, 92, 1-11. doi:10.1016/j.biochi.2009.09.018
[30] Hattrup, C.L. and Gendler, S.J. (2008) Structure and function of the cell surface (tethered) mucins. Annual Review of Physiology, 70, 431-457. doi:10.1146/annurev.physiol.70.113006.100659
[31] Yuan, S., Shi, C., Ling, R., Wang, T., Wang, H. and Han, W. (2010) Immunization with two recombinant bacillus calmette-guerin vaccines that combine the expression of multiple tandem repeats of mucin-1 and colony stimulat- ing-factor suppress breast tumor growth in mice. Journal of Cancer Research and Clinical Oncology, 136, 1359- 1367. doi:10.1007/s00432-010-0787-x
[32] Thie, H., Toleikis, L., Li, J., von Wasielewski, R., Bastert, G., Schirrmann, T., et al. (2011) Rise and fall of an Anti- -MUC1 specific antibody. PLoS ONE, 6, Article Number: e15921. doi:10.1371/journal.pone.0015921
[33] Hanash, S.M., Baik, C.S. and Kallioniemi, O. (2011) Emerging molecular biomarkers—Blood-based strategies to detect and monitor cancer. Nature Reviews Clinical Oncology, 8, 142-150. doi:10.1038/nrclinonc.2010.220
[34] Bohunicky, B. and Mousa, S.A. (2011) Biosensors: The new wave in cancer diagnosis. Nanotechnology, Science and Applications, 4, 1-10.

  
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