Breast Cancer (BC) is a highly heterogeneous disease whose most aggressive behavior is displayed by triple-negative breast cancer (TNBC), which lacks an efficient targeted therapy. Despite its controversial role, one of the proteins that having been linked with BC is Annexin A1 (AnxA1), which is a Ca binding protein that acts modulating the immune system, cell membrane organization and vesicular trafficking. In this work we analyzed tissue microarrays of BC samples and observed a higher expression of AnxA1 in TNBCs and in lymph node metastasis. We also observed a positive correlation in primary tumors between expression levels of AnxA1 and its receptor, FPR1. Despite displaying a lesser strength, this correlation also exists in BC lymph node metastasis. In agreement, we have found that AnxA1 was highly expressed and secreted in the TNBC cell line MDA-MB-231 that also expressed high levels of FPR1. Furthermore, we demonstrated, by using the specific FPR1 inhibitor Cyclosporin H (CsH) and the immunosuppressive drug Cyclosporin A (CsA), the existence of an autocrine signaling of AnxA1 through the FPR1. Such signaling, elicited by AnxA1 upon its secretion, increased the aggressiveness and survival of MDA-MB-231 cells. In this manner, we demonstrated that CsA works very efficiently as an FPR1 inhibitor. Finally, by using CsA, we demonstrated that FPR1 inhibition decreased MDA-MB-231 tumor growth and metastasis formation in nude mice. These results indicate that FPR1 inhibition could be a potential intervention strategy to manage TNBCs displaying the characteristics of MDA-MB-231 cells. FPR1 inhibition can be efficiently achieved by CsA.
Saliva biomarkers using reagent-free biophotonic technology have not been investigated as a strategy for early detection of breast cancer (BC). The attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy has been proposed as a promising tool for disease diagnosis. However, its utilization in cancer is still incipient, and currently saliva has not been used for BC screening. We have applied ATR-FTIR onto saliva from patients with breast cancer, benign breast disease, and healthy matched controls to investigate its potential use in BC diagnosis. Several salivary vibrational modes have been identified in original and second-derivative spectra. The absorbance levels at wavenumber 1041 cm−1 were significantly higher (p<0.05) in saliva of breast cancer patients compared with those of benign patients, and the ROC curve analysis of this peak showed a reasonable accuracy to discriminate breast cancer from benign and control patients. The 1433–1302.9 cm−1 band area was significantly higher (p<0.05) in saliva of breast cancer patients than in control and benign patients. This salivary ATR-FTIR spectral area was prevalidated as a potential diagnostic biomarker of BC. This spectral biomarker was able to discriminate human BC from controls with sensitivity and specificity of 90% and 80%, respectively. Besides, it was able to differentiate BC from benign disease with sensitivity and specificity of 90% and 70%, respectively. Briefly, for the first time, saliva analysis by ATR-FTIR spectroscopy has demonstrated the potential use of salivary spectral biomarkers (1041 cm−1 and 1433–1302.9 cm−1) as a novel alternative for noninvasive BC diagnosis, which could be used for screening purposes.
Annexin A1 is a 37 kDa phospholipid-binding protein that is expressed in many tissues and cell types, including leukocytes, lymphocytes and epithelial cells. Although Annexin A1 has been extensively studied for its anti-inflammatory activity, it has been shown that, in the cancer context, its activity switches from anti-inflammatory to pro-inflammatory. Remarkably, Annexin A1 shows pro-invasive and pro-tumoral properties in several cancers either by eliciting autocrine signaling in cancer cells or by inducing a favorable tumor microenvironment. Indeed, the signaling of the N-terminal peptide of AnxA1 has been described to promote the switching of macrophages to the pro-tumoral M2 phenotype. Moreover, AnxA1 has been described to prevent the induction of antigen-specific cytotoxic T cell response and to play an essential role in the induction of regulatory T lymphocytes. In this way, Annexin A1 inhibits the anti-tumor immunity and supports the formation of an immunosuppressed tumor microenvironment that promotes tumor growth and metastasis. For these reasons, in this review we aim to describe the role of Annexin A1 in the establishment of the tumor microenvironment, focusing on the immunosuppressive and immunomodulatory activities of Annexin A1 and on its interaction with the epidermal growth factor receptor.
Purpose Prostate Cancer (PCa) is one of the most common cancers in men and its early detection can provide a high chance of cure. The detection of Vitamin D Receptor (VDR) gene polymorphisms may be useful as a molecular indicator of clinical outcome, once VDR is implicated in a wide variety of biological processes including modulation of the immune response and inhibition of cancer cell growth, angiogenesis and metastasis. In this study we explored the Single Nucleotide Polymorphisms (SNPs) FokI, BsmI, ApaI and TaqI, to evaluate the susceptibility locus for PCa and verify its correlation with clinical parameters.MethodsVDR polymorphisms were detected by PCR followed by Restriction Fragment Length Polymorphism (PCR–RFLP). DNA samples were extracted from peripheral blood of 342 patients: 132 PCa, 41 Benign Prostatic Hyperplasia and 169 young healthy volunteers.Results Statistical analysis showed a noteworthy correlation among SNPs and clinical pathological features. CC genotype (TaqI) was correlated with the age at diagnosis (>58 years old), and GG (BsmI) was associated to lower Prostate-Specific Antigen (PSA) levels (<10 ng/mL). Moreover, when PCa patients were subgrouped, G allele (BsmI) significantly increased the estimated chance for PSA < 10 ng/mL, and GG/GG genotype (BsmI/ApaI) provided a 9.75 fold increased chance of patients with PCa to present lower PSA levels.ConclusionsThe polymorphisms of VDR gene showed a genotype-phenotype association and presented new correlations with different parameters as age and PSA levels.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-2009-8) contains supplementary material, which is available to authorized users.
Background: There is no biological or epidemiological data on the association between NOS3 promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of NOS3 gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage.
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