Aromatase (CYP19) expression in tumor-infiltrating lymphocytes and blood mononuclears

Lm, Berstein; Larionov, Alexey; Te, Poroshina; Ts, Zimarina; Ee, Leenman

doi:10.1007/s00432-002-0322-9

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…The tumor-infiltrating lymphocytes are able to produce and release vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor, which can induce lymphangiogenesis and angiogenesis and consequently could permit the dissemination of cancer cells through lymphatics to regional lymph nodes. [24][25][26][27][28] Bernstein et al 29 demonstrated that the aromatase (CYP19) gene is presented in tumor-infiltrating lymphocytes, and the presence of local oestrone formation could have some functional significance for the estrogendependent growth of breast cancer tissue, creating favorable environment for cancer cells. The presence of tumor-infiltrating lymphocytes in breast carcinomas and production of potentially immunoinhibitory cytokines such as IL-4, IL-10, and TGF-²1 has been demonstrated; this production by tumor-infiltrating lymphocytes in breast cancers exceeded that detected in benign breast lesions, suggesting a role for tumor-infiltrating lymphocytes in immunosuppression, creating a mechanism of immune escape for the tumor.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Infiltrating Cd4+ T Lymphocytes in Early Breast Cancer Reflect Lymph Node Involvement

Macchetti

Marana

Silva

et al. 2006

Clinics

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BACKGROUND: The role of immune system in the pathogenesis and progression of breast cancer is a subject of controversy, and this stimulated us to investigate the association of the immunophenotype of tumor-infiltrating lymphocytes in early breast cancer with the spread of tumor cells to axillary lymph nodes. METHODS: Tumor samples from 23 patients with early breast cancer from the Department of Gynecology and Obstetrics of Ribeirão Preto Medical School (USP) were obtained at the time of biopsy and submitted to an enzyme-digestion procedure for the extraction of tumor-infiltrating lymphocytes. The lymphocytes extracted were analyzed by dual-color flow cytometry with monoclonal antibodies in these combinations: CD3 FITC/CD19 PE, CD3 FITC/CD4 PE, CD3 FITC/CD8 PE, and CD16/56 PerCP, which are specific for immunophenotyping of T and B lymphocytes, helper and cytotoxic T lymphocytes, and natural killer (NK) cells. The mean percentage of these cells was used for comparing groups of patients with or without lymph node metastasis. RESULTS: The mean value for T-lymphocyte infiltration was 24.72 ± 17.37%; for B-lymphocyte infiltration, 4.22 ± 6.27%; for NK-cell infiltration, 4.41 ± 5.22%, and for CD4 + and CD8 + T-lymphocyte infiltration, 12.43 ± 10.12% and 11.30 ± 15.09%, respectively. Only mean values of T-and CD4 + T-lymphocyte infiltration were higher in the group of patients with lymph node metastasis, while no differences were noted in the other lymphocyte subpopulations. CONCLUSION: The association of tumor-infiltrating CD4 + T lymphocytes with lymph node metastasis suggests a role for these cells in the spread of neoplasia to lymph nodes in patients with early breast cancer.

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Section: Discussionmentioning

confidence: 99%

Tumor-Infiltrating Cd4+ T Lymphocytes in Early Breast Cancer Reflect Lymph Node Involvement

Macchetti

Marana

Silva

et al. 2006

Clinics

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“…It appears that the rate-limiting step of steroidogenesis, mediated by steroidogenic acute regulatory protein (StAR), functions in myeloid cells, suggesting the capacity of these cells to synthesize steroids de novo [39,40]. However, in the absence of this step in other immune cells, steroidogenesis is carried out upon the availability of downstream intermediates such as androstenedione or dehydroepiandrosterone (DHEA) [41].…”

Section: Non-nuclear-receptor-mediated Effects Of Cholesterol Metabolmentioning

confidence: 99%

Nuclear receptors, cholesterol homeostasis and the immune system

Shahoei

Nelson

2019

The Journal of Steroid Biochemistry and Molecular Biology

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Cholesterol is essential for maintaining membrane fluidity in eukaryotes. Additionally, the synthetic cascade of cholesterol results in precursor molecules important for cellular function such as lipid raft formation and protein prenylation. As such, cholesterol homeostasis is tightly regulated. Interestingly, it is now known that some cholesterol precursors and many metabolites serve as active signaling molecules, binding to different classes of receptors including the nuclear receptors. Furthermore, many cholesterol metabolites or their nuclear receptors have been implicated in the regulation of the immune system in normal physiology and disease. Therefore, in this focused review, cholesterol homeostasis and nuclear receptors involved in this regulation will be discussed, with particular emphasis on how these cascades influence the immune system.

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“…In experimental PH, dysregulated immunity in the form of deficient regulatory T-cell (Treg) activity contributes to increased inflammation [20]. Both alveolar macrophages and immune cells express steroidogenic enzymes including sulfatase and aromatase [119][120][121]. Inflammatory cytokines, prostanoids, and growth factors regulate the expression and activity of steroidogenic enzymes, and in turn, sex hormones 2-Methoxyestradiol in Pulmonary Arterial Hypertension: A New Disease Modifier DOI: http://dx.doi.org/10.5772/intechopen.86812 may influence the production and release of these autocrine/paracrine mediators [122].…”

Section: Anti-inflammatory and Immunomodulatory Effects Of 2mementioning

confidence: 99%

2-Methoxyestradiol in Pulmonary Arterial Hypertension: A New Disease Modifier

Tofovic¹,

Jackson²

2019

Interventional Pulmonology and Pulmonary Hypertension - Updates on Specific Topics [Working Title]

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Pulmonary arterial hypertension (PAH), a debilitating and incurable disease, predominantly develops in women. Estradiol metabolism leads to the production of numerous metabolites with different levels of estrogenic activity and very often opposing biological effects. Dysregulated estradiol metabolism was recently linked to the penetrance, progression, and prognosis of the disease. Ongoing clinical trials are examining the effects of estradiol synthesis/signaling inhibition in patients with PAH. In this chapter, the effects of sex, sex hormones, and estradiol metabolism on the healthy pulmonary circulation and vascular pathobiology are discussed in the light of estradiol metabolism as potential pharmacological target in PAH. The effects of estrogens and their metabolites on vascular pathobiology and disease progression, their involvement in PAH-associated diseases, and the pros and cons for interventions at different levels of estradiol metabolism are discussed. Finally, we propose that 2-methoxyestradiol (2ME), a major non-estrogenic metabolite of estradiol, mediates at least in part the beneficial effects of estradiol and that 2ME exhibits opposing effects to estradiol on several processes relevant to the underlying pathophysiology of PAH, including angiogenesis, metabolic reprograming, inflammation, and immunity. Based on cellular and in vivo effects, 2ME should be viewed as a disease modifier in women with PAH.

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Aromatase (CYP19) expression in tumor-infiltrating lymphocytes and blood mononuclears

Abstract: The data obtained suggest that aromatase gene expression is presented in TIL at a rather low level. Nevertheless, this can have some functional significance for the estrogen-dependent growth of breast cancer tissue.

Cited by 8 publications

References 26 publications

Tumor-Infiltrating Cd4+ T Lymphocytes in Early Breast Cancer Reflect Lymph Node Involvement

Tumor-Infiltrating Cd4+ T Lymphocytes in Early Breast Cancer Reflect Lymph Node Involvement

Nuclear receptors, cholesterol homeostasis and the immune system

2-Methoxyestradiol in Pulmonary Arterial Hypertension: A New Disease Modifier

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