Immunoglobulin g from breast cancer patients regulates MCF-7 cells migration and MMP-9 activity by stimulating muscarinic acetylcholine receptors.

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 M(3) and M(4) 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.

Immunoglobulin G from breast cancer patients in stage I stimulates muscarinic acetylcholine receptors in MCF7 cells and induces proliferation. Participation of nitric oxide synthase-derived nitric oxide.

INTRODUCTION: Muscarinic acetylcholine receptors (mAChR) belong to the G-protein-coupled receptor family and are extensively expressed in most cells in mammals. We had reported the expression of mAChR in murine and human breast tumors. METHODS: The presence of antibodies in the sera of patients with different tumors directed against self-proteins has been recently described. In this work, we investigated the presence of autoantibodies against mAChR in the sera of breast cancer patients in stage I (T1N0Mx-IgG). IgG purification was performed by affinity chromatography in protein G-agarose. We also studied the ability of these antibodies to modulate the proliferation of MCF-7 breast tumor cells by the MTS colorimetric assay. The ability of T1N0Mx-IgG to stimulate muscarinic signaling pathway via nitric oxide synthase was tested by Griess reaction. RESULTS: We demonstrated M(3) and M(4) receptors expression in MCF-7 cells. T1N0Mx-IgG promotes cell proliferation, mimicking the action of the muscarinic agonist carbachol. This effect was preferentially due to M(3) receptor activation in tumor cells via phospholipase C-induced nitric oxide liberation by calcium-dependent nitric oxide synthases. IgG from control patients was unable to produce this effect. DISCUSSION: IgG from patients with breast cancer in early stages could be promoting tumor progression by muscarinic activation, and its presence could be determining the prognosis of this illness.

Second look en carcinomas epitelial del ovario / look in epithelial carcinoma of the ovary

Sobre un total de 108 Carcinomas Epiteliales del Ovario tratados desde 1974 hasta la fecha, se apresentan 32 pacientes sometidas a Operaciones de Segunda Vista. Se excluyeron las Laparotomías de reestadificación y las Operaciones Citorreductivas luego del tratamiento inicial. Se clasificaron según el Estadio inicial el Tipo y Gradding histológico, así como la Quimioterapia recibida luego de la cirugía primaria. Se encontraron 22/32 casos con Second-look negativo (68,7%) y 10/32 con Second-look positivo (31,2%), cuatro positivos microscópicos (12,5%) y seis positivos macroscópicos (18,7%). Se discute el concepto de Operación de Segunda Vista, las indicaciones, el momento oportuno de su realización, la técnica a emplear y ventajas o desventajas de la misma. Se observó que el estadio inicial y el Gradding histológico tuvieron valor pronóstico en encontrar Second-look positivos. Hubo 4/22 reccurrencias (18,1%) dentro del grupo de Second-look negativos y 18/22 pacientes se encuentran libres de enfermedad aparente a la fecha (81,8%) lo que habla de la sensibilidad y especificidad del procedimiento. Se concluye en establecer la necesidad, en la actualidad, de la Operación de Segunda Vista como diagnóstico de certeza y pronóstico de la paciente

Second look en carcinomas epitelial del ovario / look in epithelial carcinoma of the ovary

Sobre un total de 108 Carcinomas Epiteliales del Ovario tratados desde 1974 hasta la fecha, se apresentan 32 pacientes sometidas a Operaciones de Segunda Vista. Se excluyeron las Laparotomías de reestadificación y las Operaciones Citorreductivas luego del tratamiento inicial. Se clasificaron según el Estadio inicial el Tipo y Gradding histológico, así como la Quimioterapia recibida luego de la cirugía primaria. Se encontraron 22/32 casos con Second-look negativo (68,7%) y 10/32 con Second-look positivo (31,2%), cuatro positivos microscópicos (12,5%) y seis positivos macroscópicos (18,7%). Se discute el concepto de Operación de Segunda Vista, las indicaciones, el momento oportuno de su realización, la técnica a emplear y ventajas o desventajas de la misma. Se observó que el estadio inicial y el Gradding histológico tuvieron valor pronóstico en encontrar Second-look positivos. Hubo 4/22 reccurrencias (18,1%) dentro del grupo de Second-look negativos y 18/22 pacientes se encuentran libres de enfermedad aparente a la fecha (81,8%) lo que habla de la sensibilidad y especificidad del procedimiento. Se concluye en establecer la necesidad, en la actualidad, de la Operación de Segunda Vista como diagnóstico de certeza y pronóstico de la paciente (AU)