Muscarinic receptors autoantibodies purified from mammary adenocarcinoma-bearing mice sera stimulate tumor progression

Fiszman, Gabriel L.; Cattaneo, Valentina; Torre, Eulalia de la; Español, Alejandro; Colombo, Lucas L.; Lustig, Eugenia Sacerdote de; Sales, Marı́a Elena

doi:10.1016/j.intimp.2006.04.007

Cited by 10 publications

(12 citation statements)

References 21 publications

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“…We had previously described the presence of autoAbs in the sera of mice LM3 tumor bearers [21]. These autoAbs recognize and activate mAChR over-express in tumor cells, and promote tumor growth and angiogenesis, revealing that mAChR could be acting as autoantigens [21]. Recently, we identified a similar population of autoAbs in the IgG fraction purified from the sera of breast cancer patients in stage I [6].…”

Section: Discussionmentioning

confidence: 96%

“…Most of the antigens identified in human tumors are self-proteins without mutations but inappropriately expressed or over-expressed [20]. We had previously described the presence of autoAbs in the sera of mice LM3 tumor bearers [21]. These autoAbs recognize and activate mAChR over-express in tumor cells, and promote tumor growth and angiogenesis, revealing that mAChR could be acting as autoantigens [21].…”

Section: Discussionmentioning

confidence: 99%

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Autoantibodies against Muscarinic Receptors in Breast Cancer: Their Role in Tumor Angiogenesis

et al. 2013

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The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10−8 M) and carbachol (10−9 M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Autoantibodies against Muscarinic Receptors in Breast Cancer: Their Role in Tumor Angiogenesis

et al. 2013

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“…Cells (2 × 10 6 ) were washed twice with PBS and lysed in 1 mL of modified RIPA buffer: 50 mM Tris-HCl; 150 mM NaCl; 1 mM NaF, EDTA and PMSF; 1% Triton X-100; 4 μg·mL −1 trypsin inhibitor; 5 μg·mL −1 aprotinin; 5 μg·mL −1 leupeptin, pH 7.4. After 1 h in an ice bath, lysates were centrifuged at 8000× g for 20 min at 4°C (Fiszman et al, 2006). Supernatants were stored at −80°C and the protein concentration was determined by the method of Bradford (1976).…”

Section: Detection Of Nos Isoforms By Western Blotmentioning

confidence: 99%

Treatment with LPS plus INF‐γ induces the expression and function of muscarinic acetylcholine receptors, modulating NIH3T3 cell proliferation: participation of NOS and COX

Español

Maddaleno

Lombardi

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSELPS and IFN-γ are potent stimuli of inflammation, a process in which fibroblasts are frequently involved. We analysed the effect of treatment with LPS plus IFN-γ on the expression and function of muscarinic acetylcholine receptors in NIH3T3 fibroblasts with regards to proliferation of these cells. We also investigated the participation of NOS and COX, and the role of NF-κB in this process. EXPERIMENTAL APPROACHNIH3T3 cells were treated with LPS (10 ng·mL ) for 72 h (iNIH3T3 cells). Cell proliferation was evaluated with MTT and protein expression by Western blot analysis. NOS and COX activities were measured by the Griess method and radioimmunoassay respectively. KEY RESULTSThe cholinoceptor agonist carbachol was more effective at stimulating proliferation in iNIH3T3 than in NIH3T3 cells, probably due to the de novo induction of M3 and M5 muscarinic receptors independently of NF-κB activation. iNIH3T3 cells produced higher amounts of NO and PGE2 than NIH3T3 cells, concomitantly with an up-regulation of NOS1 and COX-2, and with the de novo induction of NOS2/3 in inflamed cells. We also found a positive feedback between NOS and COX that could potentiate inflammation. CONCLUSIONS AND IMPLICATIONSInflammation induced the expression of muscarinic receptors and, therefore,stimulated carbachol-induced proliferation of fibroblasts. Inflammation also up-regulated the expression of NOS and COX-2, thus potentiating the effect of carbachol on NO and PGE2 production. A positive crosstalk between NOS and COX triggered by carbachol in inflamed cells points to muscarinic receptors as potential therapeutic targets in inflammation.

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“…After 1 h in ice bath, lysates were centrifuged at 6,720 g for 20 min at 4°C [14]. Supernatants were stored at -80°C, and protein concentration was determined by the method of Bradford [15].…”

Section: Nitric Oxide Productionmentioning

confidence: 99%

Nitric oxide synthase 1 and cyclooxygenase-2 enzymes are targets of muscarinic activation in normal and inflamed NIH3T3 cells

et al. 2009

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Muscarinic receptors autoantibodies purified from mammary adenocarcinoma-bearing mice sera stimulate tumor progression

Cited by 10 publications

References 21 publications

Autoantibodies against Muscarinic Receptors in Breast Cancer: Their Role in Tumor Angiogenesis

Autoantibodies against Muscarinic Receptors in Breast Cancer: Their Role in Tumor Angiogenesis

Treatment with LPS plus INF‐γ induces the expression and function of muscarinic acetylcholine receptors, modulating NIH3T3 cell proliferation: participation of NOS and COX

Nitric oxide synthase 1 and cyclooxygenase-2 enzymes are targets of muscarinic activation in normal and inflamed NIH3T3 cells

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