Correlation between biological and mechanical properties of extracellular matrix from colorectal peritoneal metastases in human tissues.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
27 07 2023
Historique:
received: 19 12 2022
accepted: 14 07 2023
medline: 31 7 2023
pubmed: 28 7 2023
entrez: 27 7 2023
Statut: epublish

Résumé

Peritoneal metastases (PM) are common routes of dissemination for colorectal cancer (CRC) and remain a lethal disease with a poor prognosis. The properties of the extracellular matrix (ECM) are important in cancer development; studying their changes is crucial to understand CRC-PM development. We studied the elastic properties of ECMs derived from human samples of normal and neoplastic PM by atomic force microscopy (AFM); results were correlated with patient clinical data and expression of ECM components related to metastatic spread. We show that PM progression is accompanied by stiffening of the ECM, increased cancer associated fibroblasts (CAF) activity and increased deposition and crosslinking in neoplastic matrices; on the other hand, softer regions are also found in neoplastic ECMs on the same scales. Our results support the hypothesis that local changes in the normal ECM can create the ground for growth and spread from the tumour of invading metastatic cells. We have found correlations between the mechanical properties (relative stiffening between normal and neoplastic ECM) of the ECM and patients' clinical data, like age, sex, presence of protein activating mutations in BRAF and KRAS genes and tumour grade. Our findings suggest that the mechanical phenotyping of PM-ECM has the potential to predict tumour development.

Identifiants

pubmed: 37500685
doi: 10.1038/s41598-023-38763-w
pii: 10.1038/s41598-023-38763-w
pmc: PMC10374531
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12175

Informations de copyright

© 2023. The Author(s).

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Auteurs

Ewelina Lorenc (E)

Dipartimento di Fisica "Aldo Pontremoli" and CIMaINa, Università degli Studi di Milano, via G. Celoria 16, 20133, Milan, Italy.

Luca Varinelli (L)

Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy.

Matteo Chighizola (M)

Dipartimento di Fisica "Aldo Pontremoli" and CIMaINa, Università degli Studi di Milano, via G. Celoria 16, 20133, Milan, Italy.

Silvia Brich (S)

Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy.

Federica Pisati (F)

Histopathology Unit, Cogentech Ltd. Benefit Corporation with a Sole Shareholder, via Adamello 16, 20139, Milan, Italy.

Marcello Guaglio (M)

Peritoneal Surface Malignancies Unit, Colon and Rectal Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy.

Dario Baratti (D)

Peritoneal Surface Malignancies Unit, Colon and Rectal Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy.

Marcello Deraco (M)

Peritoneal Surface Malignancies Unit, Colon and Rectal Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy.

Manuela Gariboldi (M)

Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy. manuela.gariboldi@istitutotumori.mi.it.

Alessandro Podestà (A)

Dipartimento di Fisica "Aldo Pontremoli" and CIMaINa, Università degli Studi di Milano, via G. Celoria 16, 20133, Milan, Italy. alessandro.podesta@mi.infn.it.

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Classifications MeSH