دورية أكاديمية
Signature of the vascular tumor microenvironment as a marker of the therapeutic response to doxorubicin in a preclinical model of osteosarcoma
| العنوان: | Signature of the vascular tumor microenvironment as a marker of the therapeutic response to doxorubicin in a preclinical model of osteosarcoma |
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| المؤلفون: | Crenn, Vincent, Amiaud, Jérôme, Gomez-Brouchet, Anne, Potiron, Vincent, Gouin, François, Rosset, Philippe, Nail, Louis-Romée Le, Vidal, Luciano, Bertin, Helios, Brion, Régis, Tran, Guillaume, Verrecchia, Franck, Corre, Isabelle, Redini, Françoise |
| المساهمون: | Sarcomes osseux et remodelage des tissus calcifiés - INSERM U1238 (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de Cancérologie de l'Ouest Angers/Nantes (UNICANCER/ICO), UNICANCER, Centre Léon Bérard Lyon, Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de Recherche en Génie Civil et Mécanique (GeM), Centre National de la Recherche Scientifique (CNRS)-NANTES UNIVERSITÉ - École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université - Institut Universitaire de Technologie Saint-Nazaire (Nantes Univ - IUT Saint-Nazaire), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - Ecole Polytechnique de l'Université de Nantes (Nantes Univ - EPUN) |
| المصدر: | ISSN: 2156-6976 ; American Journal of Cancer Research ; https://cnrs.hal.science/hal-03862019Test ; American Journal of Cancer Research, 2022, 180, pp.105709. |
| بيانات النشر: | HAL CCSD e-Century Publishing |
| سنة النشر: | 2022 |
| المجموعة: | Université de Nantes: HAL-UNIV-NANTES |
| مصطلحات موضوعية: | Osteosarcoma, microenvironment, vascularization, chemotherapy, CD31, endomucin, α-SMA, immunohistochemistry, immunofluorescence, multiplexing, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Predicting a response of osteosarcoma patients to chemotherapy, such as doxorubicin or high-dose methotrexate cocktail, remains a challenge in the clinic. Moreover, the prognostic value of currently used necrosis analysis is debatable. New markers of the therapeutic response or the prognostic response are urgently needed. The microenvironment plays a key role in the vascularization of highly heterogeneous tumors. Using the syngeneic MOS-J mouse model of osteosarcoma, we focused our study on the immunohistochemistry of tumor vascularization in order to identify new vessel markers, and to search for potential markers of the therapeutic response. Endomucin+, CD31+, and α-SMA+-positive elements were quantified in control (n=6) and doxorubicin-treated (n=6) mice in three different intra-tumor locations. We also used co-labeling to assess CD31+/Endomucin+ and CD31+/α-SMA+ co-expression. We identified a central tumor zone with a low vascularization profile for all of these markers. We identified two distinct types of vessels: CD31+/Endomucin+ vessels with a sprouting, neo-angiogenic, interlaced appearance, and CD31+/α-SMA+ vessel with a well-defined, mature structure. Doxorubicin appeared to reduce CD31+ expression in the tumor invasion front. In the doxorubicin-sensitive model, there were four times more CD31+/α-SMA+ elements than in the poorly responsive model. Therefore, we propose a methodology based on immunohistochemistry and multiplexed immunofluorescence to use endomucin as a promising new vascular marker in the osteosarcoma model. Moreover, our results suggest that CD31+/α-SMA+ vessels could be considered to be indicators of vasculature normalization and they may be used as specific markers of a good therapeutic response. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35530297; hal-03862019; https://cnrs.hal.science/hal-03862019Test; https://cnrs.hal.science/hal-03862019/documentTest; https://cnrs.hal.science/hal-03862019/file/ajcr0012-1843.pdfTest; PUBMED: 35530297; PUBMEDCENTRAL: PMC9077066 |
| الإتاحة: | https://cnrs.hal.science/hal-03862019Test https://cnrs.hal.science/hal-03862019/documentTest https://cnrs.hal.science/hal-03862019/file/ajcr0012-1843.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.2AD0D04 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |