Mapping Mechanical Properties of the Tumor Microenvironment by Laser Speckle Rheological Microscopy
| Autor: | Diane M. Tshikudi, Elena F. Brachtel, Zeinab Hajjarian, Seemantini K. Nadkarni |
|---|---|
| Přispěvatelé: | RS: GROW - R2 - Basic and Translational Cancer Biology, Pathologie |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Materials science CARCINOMA MIGRATION IMPACT Receptor expression Article Shear modulus Speckle pattern Breast cancer Neoplasms Microscopy medicine Biomarkers Tumor Image Processing Computer-Assisted Tumor Microenvironment EXTRACELLULAR-MATRIX Humans BREAST-CANCER Lymph node Mechanical Phenomena Neoplasm Staging ELASTOGRAPHY Tumor microenvironment Microscopy Confocal SIGNATURE Models Theoretical medicine.disease COLLAGEN medicine.anatomical_structure Oncology METASTASIS Neoplasm Grading Breast carcinoma Rheology Algorithms |
| Zdroj: | Cancer Research, 81(18), 4874-4885. American Association for Cancer Research Inc. Cancer Res |
| ISSN: | 0008-5472 |
| DOI: | 10.1158/0008-5472.can-20-3898 |
| Popis: | Altered mechanical properties of the tumor matrix have emerged as both the cause and consequence of breast carcinogenesis. Increased tumor stiffness has traditionally provided a viable metric to screen for malignancies via palpation or imaging. Previous studies have demonstrated that the microscale mechanical properties of the cell substrate influence tumor proliferation and invasive migration in vitro. Nevertheless, the association of the mechanical microenvironment with clinical hallmarks of aggressiveness in human breast tumors, including histopathological subtype, grade, receptor expression status, and lymph node involvement is poorly understood. This is largely due to the lack of tools for mapping tumor viscoelastic properties in clinical specimens with high spatial resolution over a large field of view (FoV). Here we introduce laser Speckle rHEologicAl micRoscopy (SHEAR) that for the first time enables mapping the magnitude viscoelastic or shear modulus, |G*(x,y,ω)|, over a range of frequencies (ω = 1–250 rad/second) in excised tumors within minutes with a spatial resolution of approximately 50 μm, over multiple cm2 FoV. Application of SHEAR in a cohort of 251 breast cancer specimens from 148 patients demonstrated that |G*(x,y,ω)| (ω = 2π rad/second) closely corresponds with histological features of the tumor, and that the spatial gradient of the shear modulus, |∇|G*(x,y,ω)||, is elevated at the tumor invasive front. Multivariate analyses established that the metrics, (|G* |) and (|∇|G* ||), measured by SHEAR are associated with prognosis. These findings implicate the viscoelastic properties of the tumor microenvironment in breast cancer prognosis and likely pave the path for identifying new modifiable targets for treatment. Significance: Laser speckle rheological microscopy establishes the links between microscale heterogeneities of viscoelasticity and histopathological subtype, tumor grade, receptor expression, as well as lymph node status in breast carcinoma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|