Neutrophil elastase-dependent cleavage compromises the tumor suppressor role of EMILIN1

Eliana Pivetta, Carla Danussi, Bruna Wassermann, Teresa Maria Elisa Modica, Lisa Del Bel Belluz, Vincenzo Canzonieri, Alfonso Colombatti, Paola Spessotto

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Proteolysis of the extracellular matrix (ECM) is a key event in tumor growth and progression. The breakdown of ECM can lead to the generation of bioactive fragments that promote cell growth and spread. EMILIN1, a multidomain glycoprotein expressed in several tissues, exerts a crucial regulatory function through the engagement of α4/α9 integrins. Unlike the majority of ECM molecules that elicit a proliferative program, the signals emitting from EMILIN1 engaged by α4/α9β1 integrins are antiproliferative. In this study, aimed to demonstrate if the suppressor role of EMILIN1 was related to its structural integrity, we tested the possibility that EMILIN1 could be specifically cleaved. Among the proteolytic enzymes released in the tumor microenvironment we showed that neutrophil elastase cleaved EMILIN1 in three/four major fragments. The consequence of this proteolytic process was the impairment of its anti-proliferative role. Accordingly, EMILIN1 was digested in sarcomas and ovarian cancers. Sarcoma specimens were infiltrated by neutrophils (PMNs) and stained positively for elastase. The present findings highlight the peculiar activity of PMN elastase in disabling EMILIN1 suppressor function.

Original languageEnglish
Pages (from-to)22-32
Number of pages11
JournalMatrix Biology
Volume34
DOIs
Publication statusPublished - Feb 2014

Fingerprint

Leukocyte Elastase
Extracellular Matrix
Integrins
Sarcoma
Neoplasms
Tumor Microenvironment
Pancreatic Elastase
Growth
Ovarian Neoplasms
Proteolysis
Glycoproteins
Neutrophils
Peptide Hydrolases

Keywords

  • Cleavage
  • EMILIN1
  • Extracellular matrix
  • Neutrophil elastase
  • Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Medicine(all)

Cite this

Neutrophil elastase-dependent cleavage compromises the tumor suppressor role of EMILIN1. / Pivetta, Eliana; Danussi, Carla; Wassermann, Bruna; Modica, Teresa Maria Elisa; Del Bel Belluz, Lisa; Canzonieri, Vincenzo; Colombatti, Alfonso; Spessotto, Paola.

In: Matrix Biology, Vol. 34, 02.2014, p. 22-32.

Research output: Contribution to journalArticle

Pivetta, E, Danussi, C, Wassermann, B, Modica, TME, Del Bel Belluz, L, Canzonieri, V, Colombatti, A & Spessotto, P 2014, 'Neutrophil elastase-dependent cleavage compromises the tumor suppressor role of EMILIN1', Matrix Biology, vol. 34, pp. 22-32. https://doi.org/10.1016/j.matbio.2014.01.018
Pivetta, Eliana ; Danussi, Carla ; Wassermann, Bruna ; Modica, Teresa Maria Elisa ; Del Bel Belluz, Lisa ; Canzonieri, Vincenzo ; Colombatti, Alfonso ; Spessotto, Paola. / Neutrophil elastase-dependent cleavage compromises the tumor suppressor role of EMILIN1. In: Matrix Biology. 2014 ; Vol. 34. pp. 22-32.
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