Investigating the contribution of hyaluronan to the breast tumour microenvironment using multiparametric MRI and MR elastography.
Date
2023-06-01ICR Author
Author
Reeves, EL
Li, J
Zormpas-Petridis, K
Boult, JKR
Sullivan, J
Cummings, C
Blouw, B
Kang, D
Sinkus, R
Bamber, JC
Jamin, Y
Robinson, SP
Type
Journal Article
Metadata
Show full item recordAbstract
Hyaluronan (HA) is a key component of the dense extracellular matrix in breast cancer, and its accumulation is associated with poor prognosis and metastasis. Pegvorhyaluronidase alfa (PEGPH20) enzymatically degrades HA and can enhance drug delivery and treatment response in preclinical tumour models. Clinical development of stromal-targeted therapies would be accelerated by imaging biomarkers that inform on therapeutic efficacy in vivo. Here, PEGPH20 response was assessed by multiparametric magnetic resonance imaging (MRI) in three orthotopic breast tumour models. Treatment of 4T1/HAS3 tumours, the model with the highest HA accumulation, reduced T1 and T2 relaxation times and the apparent diffusion coefficient (ADC), and increased the magnetisation transfer ratio, consistent with lower tissue water content and collapse of the extracellular space. The transverse relaxation rate R2 * increased, consistent with greater erythrocyte accessibility following vascular decompression. Treatment of MDA-MB-231 LM2-4 tumours reduced ADC and dramatically increased tumour viscoelasticity measured by MR elastography. Correlation matrix analyses of data from all models identified ADC as having the strongest correlation with HA accumulation, suggesting that ADC is the most sensitive imaging biomarker of tumour response to PEGPH20.
Collections
Subject
PEGPH20
breast cancer
extracellular matrix
hyaluronan
multiparametric MRI
Humans
Female
Multiparametric Magnetic Resonance Imaging
Hyaluronic Acid
Tumor Microenvironment
Elasticity Imaging Techniques
Breast Neoplasms
Magnetic Resonance Imaging
Research team
Pre-Clinical MRI
Ultrasound & Optic Imag
Language
eng
Date accepted
2023-04-14
License start date
2023-06-01
Citation
Molecular Oncology, 2023, 17 (6), pp. 1076 - 1092
Publisher
WILEY