Insight on Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix

Manuela Nebuloni, Luca Albarello, Annapaola Andolfo, Cinzia Magagnotti, Luca Genovese, Irene Locatelli, Giovanni Tonon, Erika Longhi, Pietro Zerbi, Raffaele Allevi, Alessandro Podestà, Luca Puricelli, Paolo Milani, Armando Soldarini, Andrea Salonia, Massimo Alfano

Research output: Contribution to journalArticle

Abstract

The extracellular matrix (ECM) from perilesional and colorectal carcinoma (CRC), but not healthy colon, sustains proliferation and invasion of tumor cells. We investigated the biochemical and physical diversity of ECM in pair-wised comparisons of healthy, perilesional and CRC specimens. Progressive linearization and degree of organization of fibrils was observed from healthy to perilesional and CRC ECM, and was associated with a steady increase of stiffness and collagen crosslinking. In the perilesional ECM these modifications coincided with increased vascularization, whereas in the neoplastic ECM they were associated with altered modulation of matrisome proteins, increased content of hydroxylated lysine and lysyl oxidase. This study identifies the increased stiffness and crosslinking of the perilesional ECM predisposing an environment suitable for CRC invasion as a phenomenon associated with vascularization. The increased stiffness of colon areas may represent a new predictive marker of desmoplastic region predisposing to invasion, thus offering new potential application for monitoring adenoma with invasive potential.

Original languageEnglish
Article number22522
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Mar 4 2016

ASJC Scopus subject areas

  • General

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    Nebuloni, M., Albarello, L., Andolfo, A., Magagnotti, C., Genovese, L., Locatelli, I., Tonon, G., Longhi, E., Zerbi, P., Allevi, R., Podestà, A., Puricelli, L., Milani, P., Soldarini, A., Salonia, A., & Alfano, M. (2016). Insight on Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix. Scientific Reports, 6, [22522]. https://doi.org/10.1038/srep22522