TY - JOUR
T1 - Mapping Mechanical Properties of the Tumor Microenvironment by Laser Speckle Rheological Microscopy
AU - Hajjarian, Z.
AU - Brachtel, E.F.
AU - Tshikudi, D.M.
AU - Nadkarni, S.K.
N1 - Funding Information:
Z. Hajjarian reports grants from American Society for Laser Medicine and Surgery and Eleanor and Miles Shore Faculty Development Awards Program during the conduct of the study, as well as a patent for compensation for causes of temporal fluctuations of backscattered speckle patterns in laser speckle rheology of biological fluids issued, a patent for system and methods estimation of mechanical properties and size of light-scattering particles in materials issued, a patent for optical thromboelastography systems and methods issued, a patent for laser speckle micro-rheology in characterization of biomechanical properties of tissues issued, and a patent for compensating for variations of optical properties in laser speckle microrheology of breast lesions pending. D.M. Tshikudi reports a patent for optical thromboelastography systems and methods issued. S.K. Nadkarni reports grants from
Publisher Copyright:
© 2021 American Association for Cancer Research Inc.. All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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, vertical bar G*(x,y,omega)vertical bar, over a range of frequencies (omega = 1-250 rad/second) in excised tumors within minutes with a spatial resolution of approximately 50 mm, over multiple cm2 FoV. Application of SHEAR in a cohort of 251 breast cancer specimens from 148 patients demonstrated that vertical bar G* (x,y,omega)vertical bar (omega = 2p rad/second) closely corresponds with histological features of the tumor, and that the spatial gradient of the shear modulus, vertical bar del vertical bar G* (x,y,omega)vertical bar vertical bar, is elevated at the tumor invasive front. Multivariate analyses established that the metrics, (vertical bar G*vertical bar) and (vertical bar del vertical bar G*vertical bar vertical bar|), 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.
AB - 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, vertical bar G*(x,y,omega)vertical bar, over a range of frequencies (omega = 1-250 rad/second) in excised tumors within minutes with a spatial resolution of approximately 50 mm, over multiple cm2 FoV. Application of SHEAR in a cohort of 251 breast cancer specimens from 148 patients demonstrated that vertical bar G* (x,y,omega)vertical bar (omega = 2p rad/second) closely corresponds with histological features of the tumor, and that the spatial gradient of the shear modulus, vertical bar del vertical bar G* (x,y,omega)vertical bar vertical bar, is elevated at the tumor invasive front. Multivariate analyses established that the metrics, (vertical bar G*vertical bar) and (vertical bar del vertical bar G*vertical bar vertical bar|), 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.
KW - BREAST-CANCER
KW - EXTRACELLULAR-MATRIX
KW - ELASTOGRAPHY
KW - METASTASIS
KW - SIGNATURE
KW - CARCINOMA
KW - MIGRATION
KW - COLLAGEN
KW - IMPACT
U2 - 10.1158/0008-5472.can-20-3898
DO - 10.1158/0008-5472.can-20-3898
M3 - Article
C2 - 34526347
SN - 0008-5472
VL - 81
SP - 4874
EP - 4885
JO - Cancer Research
JF - Cancer Research
IS - 18
ER -