Stromal estrogen receptor-α promotes tumor growth by normalizing an increased angiogenesis
| Autor: | Christel Pequeux, Jean-François Arnal, Silvia Blacher, Andrée Krust, Isabelle Raymond-Letron, Françoise Lenfant, Laurent Brouchet, Pierre Chambon, Marine Adlanmerini, Agnès Noël, Jean-Michel Foidart, Marie-José Fouque, Philippe Rochaix, Frédéric Boudou |
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| Přispěvatelé: | Laboratoire de Biologie des Tumeurs et du Développement, GIGA-Cancer, Université de Liège, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Département d'Anatomie-Pathologique, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Simon, Marie Francoise |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Angiogenesis Estrogen receptor Mice 0302 clinical medicine MESH: Tumor Microenvironment Tumor Microenvironment MESH: Animals Melanoma MESH: Estrogen Receptor alpha [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Mice Inbred BALB C 0303 health sciences Estradiol Neovascularization Pathologic Chemistry MESH: Gene Expression Regulation Neoplastic [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism 3. Good health Gene Expression Regulation Neoplastic Oncology 030220 oncology & carcinogenesis Female MESH: Estradiol medicine.medical_specialty Stromal cell MESH: Cell Line Tumor medicine.drug_class MESH: Mice Transgenic MESH: Melanoma MESH: Mice Inbred BALB C Mice Transgenic Vascular endothelial growth inhibitor 03 medical and health sciences MESH: Mice Inbred C57BL Cell Line Tumor Internal medicine MESH: Cell Proliferation medicine Animals MESH: Mice Cell Proliferation 030304 developmental biology Tumor microenvironment Tumor hypoxia Estrogen Receptor alpha Mice Inbred C57BL Endocrinology Estrogen Cancer cell Cancer research Stromal Cells MESH: Stromal Cells MESH: Neovascularization Pathologic MESH: Female |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 2012, 72 (12), pp.3010-9. ⟨10.1158/0008-5472.CAN-11-3768⟩ Cancer Research, 2012, 72 (12), pp.3010-9. ⟨10.1158/0008-5472.CAN-11-3768⟩ |
| ISSN: | 0008-5472 1538-7445 |
| DOI: | 10.1158/0008-5472.CAN-11-3768⟩ |
| Popis: | 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. Cancer Res; 72(12); 3010–9. ©2012 AACR. |
| Databáze: | OpenAIRE |
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