Pancreatic Cancer Presents Distinct Nanomechanical Properties During Progression

Stylianou, Andreas; Voutouri, Chrysovalantis; Mpekris, Fotios; Stylianopoulos, Triantafyllos

doi:10.1007/s10439-023-03168-3

Cited by 12 publications

(15 citation statements)

References 67 publications

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“…Our second hypothesis considers that cells need to consume glucose to proliferate and grow. Because transport of glucose depends on the tissue stiffness, one can assume that spatio-temporal patterns of glucose concentration in the acinar and ductal tissue are shaped by the local elastic field, [12,47] and elastic tissue relaxation [48][49][50][51]. Taking this into account our third hypothesis assumes that at places where cells divide and tissue expands changes are produced in the elastic field which lead to glucose concentration gradients that determine local cell proliferation rate.…”

Section: Modelmentioning

confidence: 99%

A mathematical model for pancreatic cancer during intraepithelial neoplasia

Briones-Andrade,

Ramírez-Santiago,

Romero-Arias

2024

Preprint

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Cancer is the result of complex interactions of intrinsic and extrinsic cell processes, which promote sustained proliferation, resistance to apoptosis, reprogramming and reorganization. To understand the evolution of any type of cancer it is necessary to understand the role of the microenvironmental conditions and the impact of some molecular complexes and mechanisms on certain signalling pathways. As in most cancer quantitative models, the understanding of the early onset of cancer requires a multiscale analysis of the cellular microenvironment. In this paper we analyse a multiscale model of pancreatic adenocarcinoma by modelling the cellular microenvironment through elastic cell interactions and their intercellular communication mechanisms, such as growth factors and cytokines. We focus on the low-grade dysplasia (PanIN 1) and moderate dysplasia (PanIN 2) stages of the pancreatic adenocarcinoma. To this end we propose a gene regulatory network associated with the processes of proliferation and apoptosis of pancreatic cells and its kinetics in terms delayed differential equations to mimic cell development. Likewise, we couple the cell cycle with the spatial distribution of cells and the transport of growth factors to show that the adenocarcinoma evolution is triggered by inflammatory processes. We show that the oncogene RAS may be an important target to develop anti-inflammatory strategies that limit the emergence of more aggressive adenocarcinomas.

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Section: Modelmentioning

confidence: 99%

A mathematical model for pancreatic cancer during intraepithelial neoplasia

Briones-Andrade,

Ramírez-Santiago,

Romero-Arias

2024

Preprint

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“…104) Modifications in the mechanical characteristics and makeup of TME are directly correlated with the advancement of cancer. 105) The interaction of the various TME elements causes a desmoplastic reaction that occurs in numerous solid tumors, notably pancreatic cancer, which is primarily brought on by excessive production of collagen. 105) Desmoplasia causes the tumor to harden, creates a significant obstacle to efficient drug administration, and is frequently linked to a bad prognosis.…”

Section: Afm Morphology Mechanical Properties Viscoelasticity and Can...mentioning

confidence: 99%

Recent advances and biophysical applications of atomic force microscopy in cancer research: An overview

Sampath Kumar

2024

Preprint

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The implementation of atomic force microscopy (AFM) in cancer detection investigations has been made possible by new developments. Living cells' physical and chemical characteristics fluctuate anytime their physiological environments are modified. Consequently, such physical and chemical traits may represent intricate biological functions happening within cells. The shape, flexibility, and adhesive characteristics of cells can alter while they are going through the tumorigenesis phase and are driven by environmental factors. In settings that are close to physiological, AFM can carry out surface mapping and ultrastructural characterization of live cells with atomic-level resolution, as well as capturing force spectroscopy data that enables the investigation of the mechanical characteristics of cells. As a result, high resolution studies concerning the structure and mechanical attributes of cancer cells may benefit from the application of AFM. The principles of operation theory, mode of operation, and technical characteristics of AFM are presented in this paper, along with its various applications and future possibilities in cancer studies.

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“…Most recently, Stylianou et al characterized the distinct nanomechanical properties of healthy pancreas tissue and pancreatic tumors over various stages of progression [ 61 ]. Unsurprisingly, the Young’s modulus increases as the cancer progresses, and the elastic distribution of normal pancreas tissue has a single peak, whereas pancreatic tumors have distinct lower elasticity peaks and higher elasticity peaks that relate to cancer cell softening and desmoplasia, respectively [ 61 ]. By combining AFM with polarized light microscopy of picrosirius red-stained tissues, the authors also show that the higher elastic values are due to measurements collected in collagen-rich areas of the tissue.…”

Section: Application Of Atomic Force Microscopy To Study Cancer Patho...mentioning

confidence: 99%

“…By combining AFM with polarized light microscopy of picrosirius red-stained tissues, the authors also show that the higher elastic values are due to measurements collected in collagen-rich areas of the tissue. These findings open the possibility of developing novel mechanobiomarkers [ 61 ]. AFM has also been previously combined with other microscopy techniques to study cells and tissues, such as optical microscopy, second-harmonic generation, and scanning electron microscopy, as reviewed in ref.…”

Section: Application Of Atomic Force Microscopy To Study Cancer Patho...mentioning

confidence: 99%

Atomic Force Microscopy Methods to Measure Tumor Mechanical Properties

Najera

Rosenberger

Datta

2023

Cancers

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Atomic force microscopy (AFM) is a popular tool for evaluating the mechanical properties of biological materials (cells and tissues) at high resolution. This technique has become particularly attractive to cancer researchers seeking to bridge the gap between mechanobiology and cancer initiation, progression, and treatment resistance. The majority of AFM studies thus far have been extensively focused on the nanomechanical characterization of cells. However, these approaches fail to capture the complex and heterogeneous nature of a tumor and its host organ. Over the past decade, efforts have been made to characterize the mechanical properties of tumors and tumor-bearing tissues using AFM. This has led to novel insights regarding cancer mechanopathology at the tissue scale. In this Review, we first explain the principles of AFM nanoindentation for the general study of tissue mechanics. We next discuss key considerations when using this technique and preparing tissue samples for analysis. We then examine AFM application in characterizing the mechanical properties of cancer tissues. Finally, we provide an outlook on AFM in the field of cancer mechanobiology and its application in the clinic.

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Pancreatic Cancer Presents Distinct Nanomechanical Properties During Progression

Cited by 12 publications

References 67 publications

A mathematical model for pancreatic cancer during intraepithelial neoplasia

A mathematical model for pancreatic cancer during intraepithelial neoplasia

Recent advances and biophysical applications of atomic force microscopy in cancer research: An overview

Atomic Force Microscopy Methods to Measure Tumor Mechanical Properties

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