Hypoxia Inducible Factors Modify Collagen I Fibers in MDA-MB-231 Triple Negative Breast Cancer Xenografts12

Autor: Goggins, Eibhlin, Kakkad, Samata, Mironchik, Yelena, Jacob, Desmond, Wildes, Flonne, Krishnamachary, Balaji, Bhujwalla, Zaver M.
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Original article
Col1
Collagen I
SMA
Smooth Muscle Actin
MT-MMP
Membrane-Type Matrix Metalloproteinase
Apoptosis
Triple Negative Breast Neoplasms
SHG
Second Harmonic Generation
qRT-PCR
Quantitative Real Time Polymerase Chain Reaction
LOX
Lysyl Oxidase
TNBC
Triple Negative Breast Cancer
Collagen Type I
Protein-Lysine 6-Oxidase
Mice
DAB
3
3′-diaminobenzedine
Basic Helix-Loop-Helix Transcription Factors
Biomarkers
Tumor
Tumor Cells
Cultured
Tumor Microenvironment
Animals
Humans
ECM
Extracellular Matrix
Cell Proliferation
TME
Tumor Microenvironment
Elastic Tissue
Hypoxia-Inducible Factor 1
alpha Subunit
Xenograft Model Antitumor Assays
MMP
Matrix Metalloproteinase
Cell Hypoxia
Gene Expression Regulation
Neoplastic
P4H
Prolyl Hydroxylase
DS
Double Silenced
HIF
Hypoxia Inducible Factor
H&E
Hematoxylin and eosin
Female
Zdroj: Neoplasia (New York, N.Y.)
ISSN: 1476-5586
1522-8002
Popis: 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.
Databáze: OpenAIRE
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