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Analysis of Hypoxia and the Hypoxic Response in Tumor Xenografts.
- Source :
-
Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2018; Vol. 1742, pp. 283-300. - Publication Year :
- 2018
-
Abstract
- Solid tumors are often characterized by insufficient oxygen supply (hypoxia), as a result of inadequate vascularization, which cannot keep up with the rapid growth rate of the tumor. Tumor hypoxia is a negative prognostic and predictive factor and is associated with a more aggressive phenotype in various tumor entities. Activation of the hypoxic response in tumors, which is centered around the hypoxia-inducible transcription factors (HIFs), has been causally linked to neovascularization, increased radio- and chemoresistance, altered cell metabolism, genomic instability, increased metastatic potential, and tumor stem cell characteristics. Thus, the hypoxic tumor microenvironment represents a main driving force for tumor progression and a potential target for therapeutic interventions. Here, we describe several methods for the analysis of tumor hypoxia and the hypoxic response in vivo in tumor xenograft models. These methods can be applied to various tumor models, including brain tumor xenotransplants, and allow simultaneously determining the extent and distribution of hypoxia within the tumor, analyzing HIF levels by immunohistochemistry and immunoblot, and quantifying the expression of HIF target genes in tumor tissue. The combination of these approaches provides an important tool to assess the role of the hypoxic tumor microenvironment in vivo.
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Brain Neoplasms genetics
Brain Neoplasms metabolism
Cell Hypoxia
Cell Line, Tumor
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glioblastoma genetics
Glioblastoma metabolism
Humans
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Mice
Neoplasm Transplantation
Tumor Microenvironment
Basic Helix-Loop-Helix Transcription Factors metabolism
Brain Neoplasms surgery
Gene Regulatory Networks
Glioblastoma surgery
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1940-6029
- Volume :
- 1742
- Database :
- MEDLINE
- Journal :
- Methods in molecular biology (Clifton, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 29330809
- Full Text :
- https://doi.org/10.1007/978-1-4939-7665-2_25