A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model
Autor: | Raffaele A. Calogero, Matteo Curtarello, Marco Macagno, Aichi Msaki, Stefano Indraccolo, Alberto Amadori, Federica Cavallo, Anna Pastò, Maddalena Arigoni, Giuseppina Barutello |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Carcinogenesis Angiogenesis Mice Transgenic medicine.disease_cause Her2-neu Her2/neu HER2/neu Metastasis Mice 03 medical and health sciences breast cancer 0302 clinical medicine Breast cancer DTC hypoxia tumorigenesis medicine Animals Mice Inbred BALB C biology business.industry Mammary Neoplasms Experimental Cancer Her2/Neu Hypoxia Tumorigenesis Oncology medicine.disease Cell Hypoxia 030104 developmental biology medicine.anatomical_structure Tumor progression 030220 oncology & carcinogenesis Disease Progression Cancer research biology.protein Female Bone marrow business Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | // Aichi Msaki 1 , Anna Pasto 1 , Matteo Curtarello 1 , Maddalena Arigoni 2 , Giuseppina Barutello 2 , Raffaele Adolfo Calogero 2 , Marco Macagno 2 , Federica Cavallo 2 , Alberto Amadori 1, 3, * , Stefano Indraccolo 1, * 1 Istituto Oncologico Veneto - IRCCS, Padova, Italy 2 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy 3 Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy * These authors have contributed equally to this work Correspondence to: Stefano Indraccolo, email: stefano.indraccolo@unipd.it Keywords: breast cancer, Her2/neu, hypoxia, DTC, tumorigenesis Received: July 30, 2015 Accepted: March 31, 2016 Published: April 20, 2016 ABSTRACT Metastasis is the final stage of cancer progression. Some evidence indicates that tumor cell dissemination occurs early in the natural history of cancer progression. Disseminated tumor cells (DTC) have been described in the bone marrow (BM) of cancer patients as well as in experimental models, where they correlate with later development of metastasis. However, little is known about the tumorigenic features of DTC obtained at different time points along tumor progression. Here, we found that early DTC isolated from BM of 15-17 week-old Her2/neu transgenic (BALB-neuT) mice were not tumorigenic in immunodeficient mice. In contrast, DTC-derived tumors were easily detectable when late DTC obtained from 19-22 week-old BALB-neuT mice were injected. Angiogenesis, which contributes to regulate tumor dormancy, appeared dispensable to reactivate late DTC, although it accelerated growth of secondary DTC tumors. Compared with parental mammary tumors, gene expression profiling disclosed a distinctive transcriptional signature of late DTC tumors which was enriched for hypoxia-related transcripts and was maintained in ex-vivo cell culture. Altogether, these findings highlight a different tumorigenic potential of early and late DTC in the BALB-neuT model and describe a HIF-1α-related transcriptional signature in DTC tumors, which may render DTC angiogenesis-competent, when placed in a favourable environment. |
Databáze: | OpenAIRE |
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