Dataset Information

Visualization and Quantification of the Extracellular Matrix in Prostate Cancer Using an Elastin Specific Molecular Probe.

ABSTRACT: Human prostate cancer (PCa) is a type of malignancy and one of the most frequently diagnosed cancers in men. Elastin is an important component of the extracellular matrix and is involved in the structure and organization of prostate tissue. The present study examined prostate cancer in a xenograft mouse model using an elastin-specific molecular probe for magnetic resonance molecular imaging. Two different tumor sizes (500 mm3 and 1000 mm3) were compared and analyzed by MRI in vivo and histologically and analytically ex vivo. The T1-weighted sequence was used in a clinical 3-T scanner to calculate the relative contrast enhancement before and after probe administration. Our results show that the use of an elastin-specific probe enables better discrimination between tumors and surrounding healthy tissue. Furthermore, specific binding of the probe to elastin fibers was confirmed by histological examination and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Smaller tumors showed significantly higher signal intensity (p > 0.001), which correlates with the higher proportion of elastin fibers in the histological evaluation than in larger tumors. A strong correlation was seen between relative enhancement (RE) and Elastica-van Gieson staining (R2 = 0.88). RE was related to inductively coupled plasma-mass spectrometry data for Gd and showed a correlation (R2 = 0.78). Thus, molecular MRI could become a novel quantitative tool for the early evaluation and detection of PCa.

SUBMITTER: Kader A

PROVIDER: S-EPMC8615039 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Visualization and Quantification of the Extracellular Matrix in Prostate Cancer Using an Elastin Specific Molecular Probe.

Kader Avan A Brangsch Julia J Reimann Carolin C Kaufmann Jan O JO Mangarova Dilyana B DB Moeckel Jana J Adams Lisa C LC Zhao Jing J Saatz Jessica J Traub Heike H Buchholz Rebecca R Karst Uwe U Hamm Bernd B Makowski Marcus R MR

Biology 20211122 11

Human prostate cancer (PCa) is a type of malignancy and one of the most frequently diagnosed cancers in men. Elastin is an important component of the extracellular matrix and is involved in the structure and organization of prostate tissue. The present study examined prostate cancer in a xenograft mouse model using an elastin-specific molecular probe for magnetic resonance molecular imaging. Two different tumor sizes (500 mm<sup>3</sup> and 1000 mm<sup>3</sup>) were compared and analyzed by MRI ...[more]

PMID: 34827210

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Project description:The complex network structure of elastin and collagen extracellular matrix (ECM) forms the primary load bearing components in the arterial wall. The structural and mechanobiological interactions between elastin and collagen are important for properly functioning arteries. Here, we examined the elastin and collagen organization, realignment, and recruitment by coupling mechanical loading and multiphoton imaging. Two-photon excitation fluorescence and second harmonic generation methods were performed with a multiphoton video-rate microscope to capture real time changes to the elastin and collagen structure during biaxial deformation. Enzymatic removal of elastin was performed to assess the structural changes of the remaining collagen structure. Quantitative analysis of the structural changes to elastin and collagen was made using a combination of two-dimensional fast Fourier transform and fractal analysis, which allows for a more complete understanding of structural changes. Our study provides new quantitative evidence, to our knowledge on the sequential engagement of different arterial ECM components in response to mechanical loading. The adventitial collagen exists as large wavy bundles of fibers that exhibit fiber engagement after 20% strain. The medial collagen is engaged throughout the stretching process, and prominent elastic fiber engagement is observed up to 20% strain after which the engagement plateaus. The fiber orientation distribution functions show remarkably different changes in the ECM structure in response to mechanical loading. The medial collagen shows an evident preferred circumferential distribution, however the fiber families of adventitial collagen are obscured by their waviness at no or low mechanical strains. Collagen fibers in both layers exhibit significant realignment in response to unequal biaxial loading. The elastic fibers are much more uniformly distributed and remained relatively unchanged due to loading. Removal of elastin produces similar structural changes in collagen as mechanical loading. Our study suggests that the elastic fibers are under tension and impart an intrinsic compressive stress on the collagen.

Dataset Information

Visualization and Quantification of the Extracellular Matrix in Prostate Cancer Using an Elastin Specific Molecular Probe.

Publications

Visualization and Quantification of the Extracellular Matrix in Prostate Cancer Using an Elastin Specific Molecular Probe.

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