Hypoxia Inducible Factors Modify Collagen I Fibers in MDA-MB-231 Triple Negative Breast Cancer Xenografts.
Neoplasia
; 20(2): 131-139, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29247885
ABSTRACT
Hypoxia inducible factors (HIFs) are transcription factors that mediate the response of cells to hypoxia. HIFs have wide-ranging effects on metabolism, the tumor microenvironment (TME) and the extracellular matrix (ECM). Here we investigated the silencing effects of two of the three known isoforms, HIF-1α and HIF-2α, on collagen 1 (Col1) fibers, which form a major component of the ECM of tumors. Using a loss-of-function approach for HIF-1α or 2α or both HIF-1α and 2α, we identified a relationship between HIFs and Col1 fibers in MDA-MB-231 tumors. Tumors derived from MDA-MB-231 cells with HIF-1α or 2α or both HIF-1α and 2α silenced contained higher percent fiber volume and lower inter-fiber distance compared to tumors derived from empty vector MDA-MB-231 cells. Depending upon the type of silencing, we observed changes in Col1 degrading enzymes, and enzymes involved in Col1 synthesis and deposition. Additionally, a reduction in lysyl oxidase protein expression in HIF-down-regulated tumors suggests that more non-cross-linked fibers were present. Collectively these results identify the role of HIFs in modifying the ECM and the TME and provide new insights into the effects of hypoxia on the tumor ECM.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
/
Regulação Neoplásica da Expressão Gênica
/
Colágeno Tipo I
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Tecido Elástico
/
Fatores de Transcrição Hélice-Alça-Hélice Básicos
/
Subunidade alfa do Fator 1 Induzível por Hipóxia
/
Neoplasias de Mama Triplo Negativas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Neoplasia
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos