The Mechanical Microenvironment in Breast Cancer

Pratt, Stephen J.; Lee, Rachel; Martin, Stuart S.

doi:10.3390/cancers12061452

Cited by 41 publications

(26 citation statements)

References 214 publications

(281 reference statements)

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“…The mechanobiology focuses on the interaction between cells and physical forces, including stiffness, interstitial fluid pressure and solid stress, which can alter the signal transduction and biological responses [ 127 ]. Mechanotransduction signaling may be dysregulated in cancer, for instance the tissue stiffness may represent a risk factor for the development of breast cancer [ 128 ].…”

Section: Fak As a Mechanotransducer In Breast Cancermentioning

confidence: 99%

Focal Adhesion Kinase Fine Tunes Multifaced Signals toward Breast Cancer Progression

Rigiracciolo

Cirillo

Talia

et al. 2021

Cancers

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Breast cancer represents the most common diagnosed malignancy and the main leading cause of tumor-related death among women worldwide. Therefore, several efforts have been made in order to identify valuable molecular biomarkers for the prognosis and prediction of therapeutic responses in breast tumor patients. In this context, emerging discoveries have indicated that focal adhesion kinase (FAK), a non-receptor tyrosine kinase, might represent a promising target involved in breast tumorigenesis. Of note, high FAK expression and activity have been tightly correlated with a poor clinical outcome and metastatic features in several tumors, including breast cancer. Recently, a role for the integrin-FAK signaling in mechanotransduction has been suggested and the function of FAK within the breast tumor microenvironment has been ascertained toward tumor angiogenesis and vascular permeability. FAK has been also involved in cancer stem cells (CSCs)-mediated initiation, maintenance and therapeutic responses of breast tumors. In addition, the potential of FAK to elicit breast tumor-promoting effects has been even associated with the capability to modulate immune responses. On the basis of these findings, several agents targeting FAK have been exploited in diverse preclinical tumor models. Here, we recapitulate the multifaceted action exerted by FAK and its prognostic significance in breast cancer. Moreover, we highlight the recent clinical evidence regarding the usefulness of FAK inhibitors in the treatment of breast tumors.

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Section: Fak As a Mechanotransducer In Breast Cancermentioning

confidence: 99%

Focal Adhesion Kinase Fine Tunes Multifaced Signals toward Breast Cancer Progression

Rigiracciolo

Cirillo

Talia

et al. 2021

Cancers

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“…The fascial continuum, solid and fluid, is a web, and any stimulus present cannot escape because, regardless of the nature of the stressor, the whole network becomes aware of it and adapts. The cellular and extracellular environment are influenced by mechanical-metabolic stimuli (mechanoreciprocity), and among these stressors, we find the forces of body fluids [ 29 ]. We know that an increase in stiffness of the mammary gland tissue or an increase in collagen alters the mechano-metabolic environment, favoring the formation of tumors [ 29 ].…”

Section: Reviewmentioning

confidence: 99%

“…The cellular and extracellular environment are influenced by mechanical-metabolic stimuli (mechanoreciprocity), and among these stressors, we find the forces of body fluids [ 29 ]. We know that an increase in stiffness of the mammary gland tissue or an increase in collagen alters the mechano-metabolic environment, favoring the formation of tumors [ 29 ]. The increase in fluid pressure inside, around, and between cells is another important factor in the increase in the stiffness of the mammary gland (and other tissues) and is considered another potentially pathogenic factor (Figure 1 ) [ 29 , 30 ].…”

Section: Reviewmentioning

confidence: 99%

“…We know that an increase in stiffness of the mammary gland tissue or an increase in collagen alters the mechano-metabolic environment, favoring the formation of tumors [29]. The increase in fluid pressure inside, around, and between cells is another important factor in the increase in the stiffness of the mammary gland (and other tissues) and is considered another potentially pathogenic factor (Figure 1) [29,30]. Photograph by Bruno Bordoni.…”

Section: Review Fascial Tissue Embryology: Liquid Fasciamentioning

confidence: 99%

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Fascial Nomenclature: Update 2021, Part 2

Bordoni¹,

Escher²,

Tobbi³

et al. 2021

Cureus

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The fascial continuum is a topic of debate, in particular, its classification into a nomenclature that researchers and medical figures can agree on. Most likely, the difficulty in finding the uniqueness of this topic lies in the fact that only some scientific figures with certain specialties write articles to state their point of view. We know, however, that a matter that involves the human body cannot be taken into consideration only by some scientific arguments, but by all the notions capable of completing a multidisciplinary and impartial vision. The fascia, too often, becomes a destination for earning and selling, to the detriment of the entire scientific community. The second part of the article on fascial nomenclature tries to obtain a new definition of what could be considered the fascial continuum, based on the most innovative information in the literature; the ultimate goal is to give free reflections on the subject in full intellectual freedom.

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“…It is increasingly recognized that biomechanics of solid tumors affects their growth, invasion, and resistance to treatment [ 1 , 2 , 3 , 4 ]. The adverse role of tumor biomechanical properties has been observed in various tumors, including carcinomas of the liver, pancreas, breast, and colon [ 1 , 5 , 6 , 7 , 8 ]. The abnormal biomechanical characteristics of malignant tumors include high stiffness or viscoelasticity, solid stress, and interstitial fluid pressure.…”

Section: Introductionmentioning

confidence: 99%

Tumor Solid Stress: Assessment with MR Elastography under Compression of Patient-Derived Hepatocellular Carcinomas and Cholangiocarcinomas Xenografted in Mice

Pagé

Tardieu

Gennisson

et al. 2021

Cancers

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Malignant tumors have abnormal biomechanical characteristics, including high viscoelasticity, solid stress, and interstitial fluid pressure. Magnetic resonance (MR) elastography is increasingly used to non-invasively assess tissue viscoelasticity. However, solid stress and interstitial fluid pressure measurements are performed with invasive methods. We studied the feasibility and potential role of MR elastography at basal state and under controlled compression in assessing altered biomechanical features of malignant liver tumors. MR elastography was performed in mice with patient-derived, subcutaneously xenografted hepatocellular carcinomas or cholangiocarcinomas to measure the basal viscoelasticity and the compression stiffening rate, which corresponds to the slope of elasticity versus applied compression. MR elastography measurements were correlated with invasive pressure measurements and digital histological readings. Significant differences in MR elastography parameters, pressure, and histological measurements were observed between tumor models. In multivariate analysis, collagen content and interstitial fluid pressure were determinants of basal viscoelasticity, whereas solid stress, in addition to collagen content, cellularity, and tumor type, was an independent determinant of compression stiffening rate. Compression stiffening rate had high AUC (0.87 ± 0.08) for determining elevated solid stress, whereas basal elasticity had high AUC for tumor collagen content (AUC: 0.86 ± 0.08). Our results suggest that MR elastography compression stiffening rate, in contrast to basal viscoelasticity, is a potential marker of solid stress in malignant liver tumors.

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The Mechanical Microenvironment in Breast Cancer

Cited by 41 publications

References 214 publications

Focal Adhesion Kinase Fine Tunes Multifaced Signals toward Breast Cancer Progression

Focal Adhesion Kinase Fine Tunes Multifaced Signals toward Breast Cancer Progression

Fascial Nomenclature: Update 2021, Part 2

Tumor Solid Stress: Assessment with MR Elastography under Compression of Patient-Derived Hepatocellular Carcinomas and Cholangiocarcinomas Xenografted in Mice

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