دورية أكاديمية
Stromal estrogen receptor-α promotes tumor growth by normalizing an increased angiogenesis.
| العنوان: | Stromal estrogen receptor-α promotes tumor growth by normalizing an increased angiogenesis. |
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| المؤلفون: | Péqueux, Christel, Raymond-Letron, Isabelle, Blacher, Silvia, Boudou, Frédéric, Adlanmerini, Marine, Fouque, Marie-José, Rochaix, Philippe, Noël, Agnès, Foidart, Jean-Michel, Krust, Andrée, Chambon, Pierre, Brouchet, Laurent, Arnal, Jean-François, Lenfant, Françoise |
| المساهمون: | Laboratoire de Biologie des Tumeurs et du Développement, GIGA-Cancer, Université de Liège, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 0008-5472. |
| بيانات النشر: | HAL CCSD American Association for Cancer Research |
| سنة النشر: | 2012 |
| المجموعة: | Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| مصطلحات موضوعية: | MESH: Animals, MESH: Cell Line, Tumor, MESH: Mice, Inbred C57BL, Transgenic, MESH: Neovascularization, Pathologic, MESH: Stromal Cells, MESH: Tumor Microenvironment, MESH: Cell Proliferation, MESH: Estradiol, MESH: Estrogen Receptor alpha, MESH: Female, MESH: Gene Expression Regulation, Neoplastic, MESH: Melanoma, Inbred BALB C, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism |
| الوصف: | International audience ; Estrogens directly promote the growth of breast cancers that express the estrogen receptor α (ERα). However, the contribution of stromal expression of ERα in the tumor microenvironment to the protumoral effects of estrogen has never been explored. In this study, we evaluated the molecular and cellular mechanisms by which 17β-estradiol (E2) impacts the microenvironment and modulates tumor development of ERα-negative tumors. Using different mouse models of ER-negative cancer cells grafted subcutaneously into syngeneic ovariectomized immunocompetent mice, we found that E2 potentiates tumor growth, increases intratumoral vessel density, and modifies tumor vasculature into a more regularly organized structure, thereby improving vessel stabilization to prevent tumor hypoxia and necrosis. These E2-induced effects were completely abrogated in ERα-deficient mice, showing a critical role of host ERα. Notably, E2 did not accelerate tumor growth when ERα was deficient in Tie2-positive cells, even in mice grafted with wild-type bone marrow. These results were extended by clinical evidence of ERα-positive stromal cell labeling in the microenvironment of human breast cancers. Together, our findings therefore show that E2 promotes the growth of ERα-negative cancer cells through the activation of stromal ERα (extra-hematopoietic Tie-2 positive cells), which normalizes tumor angiogenesis and allows an adaptation of blood supply to tumors, thereby preventing hypoxia and necrosis. These findings significantly deepen mechanistic insights into the impact of E2 on tumor development with potential consequences for cancer treatment. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/22523036; inserm-00732460; https://inserm.hal.science/inserm-00732460Test; PUBMED: 22523036 |
| DOI: | 10.1158/0008-5472.CAN-11-3768 |
| الإتاحة: | https://doi.org/10.1158/0008-5472.CAN-11-3768Test https://inserm.hal.science/inserm-00732460Test |
| رقم الانضمام: | edsbas.22EF823B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1158/0008-5472.CAN-11-3768 |
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