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: | Pequeux, Christel, Raymond-Letron, I, Blacher, Silvia, Boudou, F, Adlanmerini, Marine, Fouque, MJ, Rochaix, P, Noël, Agnès, Foidart, Jean-Michel, Krust, A, Chambon, P, Brouchet, L, Arnal, JF, Lenfant, FB |
| المصدر: | Cancer Research, 72 (12), 3010-3019 (2012) |
| بيانات النشر: | American Association for Cancer Research, Inc. (AACR) |
| سنة النشر: | 2012 |
| المجموعة: | University of Liège: ORBi (Open Repository and Bibliography) |
| مصطلحات موضوعية: | ERalpha, normalization, angiogenesis, tumor microenvironment, endothelial, hypoxia, necrosis, Life sciences, Biochemistry, biophysics & molecular biology, Sciences du vivant, Biochimie, biophysique & biologie moléculaire |
| الوصف: | peer reviewed ; Estrogens directly promote the growth of breast cancers that express the Estrogen Receptor (ERalpha). However, the contribution of stromal expression of ERalpha in the tumor microenvironment to the pro-tumoral effects of estrogen has never been explored. In this study, we evaluated the molecular and cellular mechanisms by which 17beta-estradiol (E2) impacts the microenvironment and modulates tumor development of ERalpha-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 ERalpha-deficient mice, demonstrating a critical role of host ERα. Notably, E2 did not accelerate tumor growth when ERalpha was deficient in Tie2- positive cells, but still expressed by bone marrow derived cells. These results were extended by clinical evidence of ERalpha-positive stromal cell labeling in the microenvironment of human breast cancers. Together, our findings therefore suggest that E2 promotes the growth of ERalpha-negative cancer cells through the activation of stromal ERα (not hematopoiteic but Tie2-dependent expression of ERalpha), which normalizes tumor angiogenesis and allows an adaptation of blood supply to tumor demand 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 |
| تدمد: | 0008-5472 1538-7445 |
| العلاقة: | info:eu-repo/grantAgreement/EC/FP7/201279; urn:issn:0008-5472; urn:issn:1538-7445; https://orbi.uliege.be/handle/2268/124721Test; info:hdl:2268/124721; https://orbi.uliege.be/bitstream/2268/124721/1/Pequeux%20C%20Cancer%20Res-2012.pdfTest; scopus-id:2-s2.0-84862539695; info:pmid:22523036 |
| DOI: | 10.1158/0008-5472.CAN-11-3768 |
| الإتاحة: | https://doi.org/10.1158/0008-5472.CAN-11-3768Test https://orbi.uliege.be/handle/2268/124721Test https://orbi.uliege.be/bitstream/2268/124721/1/Pequeux%20C%20Cancer%20Res-2012.pdfTest |
| حقوق: | open access ; http://purl.org/coar/access_right/c_abf2Test ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.DE0D8584 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00085472 15387445 |
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| DOI: | 10.1158/0008-5472.CAN-11-3768 |