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Immunoglobulin G from Breast Cancer Patients Regulates MCF-7 Cells Migration and MMP-9 Activity by Stimulating Muscarinic Acetylcholine Receptors

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Abstract

Purpose

We have previously reported the expression of muscarinic acetylcholine receptors (mAChR) in human breast tumors. The activation of these receptors triggered tumor cell proliferation. Considering that invasion and metastasis is the major cause of death in cancer, we investigated the action of autoantibodies against mAChR derived from breast cancer patients in stage I (T1N0Mx-IgG) on MCF-7 cells migration and metalloproteinase-9 (MMP-9) activity. We also analyzed the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.

Methods

Immunoglobulin G (IgG) was purified by chromatography in protein G-agarose from blood samples of breast cancer patients obtained under informed consent. Migration was assayed by an in vitro wound assay. MMP-9 activity was quantified by zymography.

Results

T1N0Mx-IgG promoted tumor cell migration and increased MMP9 activity mimicking the action of the muscarinic agonist carbachol. This effect was reduced not only by the presence of atropine but also by 4-DAMP or tropicamide, antagonists for M3 and M4 mAChR subtypes respectively. The actions of T1N0Mx-IgG and carbachol on MCF-7 cells, involved the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.

Conclusions

IgG from breast cancer patients in stage I could be promoting tumor progression by regulating migration and MMP-9 activity in tumor cells via mAChR activation. The presence of these autoantibodies could be determining the prognosis of breast cancer in these patients.

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Acknowledgments

The authors want to thank Mrs. María Ester Castro for her excellent technical assistance. This work was supported by grants from the University of Buenos Aires (UBACYT M064) and from the National Agency for Scientific and Technology Promotion (ANPCyT) (PICT 2006-485). Drs. Gabriela Lombardi and María Elena Sales are established investigators at the National Research Council of Argentina (CONICET). Dr. Laura T. Pelegrina is a fellow from CONICET.

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Authors and Affiliations

  1. Centro de Estudios Farmacológicos y Botánicos (CEFYBO)-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 piso 16, Buenos Aires, CP 1121, Argentina

    Laura T. Pelegrina, María Gabriela Lombardi & María E. Sales

  2. Instituto de Oncología A.H. Roffo, Universidad de Buenos Aires, Av. San Martín 5481, Buenos Aires, CP1428, Argentina

    Gabriel L. Fiszman, María E. Azar & Carlos Cresta Morgado

Authors
  1. Laura T. Pelegrina
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  2. María Gabriela Lombardi
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  3. Gabriel L. Fiszman
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  4. María E. Azar
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  5. Carlos Cresta Morgado
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  6. María E. Sales
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Correspondence to María E. Sales.

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Pelegrina, L.T., Lombardi, M.G., Fiszman, G.L. et al. Immunoglobulin G from Breast Cancer Patients Regulates MCF-7 Cells Migration and MMP-9 Activity by Stimulating Muscarinic Acetylcholine Receptors. J Clin Immunol 33, 427–435 (2013). https://doi.org/10.1007/s10875-012-9804-y

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  • DOI: https://doi.org/10.1007/s10875-012-9804-y

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