A biomimetic 3D model of hypoxia-driven cancer progression

Chiara Liverani, Alessandro De Vita, Silvia Minardi, Yibin Kang, Laura Mercatali, Dino Amadori, Alberto Bongiovanni, Federico La Manna, Toni Ibrahim, Ennio Tasciotti

Research output: Contribution to journalArticle

Abstract

The fate of tumors depends both on the cancer cells’ intrinsic characteristics and on the environmental conditions where the tumors reside and grow. Engineered in vitro models have led to significant advances in cancer research, allowing the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. Here we present a biomimetic cancer model based on a collagen matrix synthesized through a biologically inspired process. We compared in this environment the responses of two breast tumor lineages characterized by different molecular patterns and opposite clinical behaviors: MCF-7 that belong to the luminal A subtype connected to an indolent course, and basal-like MDA-MB-231 connected to high-grade and aggressive disease. Cancer cells in the biomimetic matrix recreate a hypoxic environment that affects their growth dynamics and phenotypic features. Hypoxia induces apoptosis and the selection of aggressive cells that acquire expression signatures associated with glycolysis, angiogenesis, cell-matrix interaction, epithelial to mesenchymal transition and metastatic ability. In response to hypoxia MDA-MB-231 migrate on the collagen fibrils and undergo cellular senescence, while MCF-7 do not exhibit these behaviors. Our biomimetic model mimics the evolution of tumors with different grade of aggressiveness fostered by a hypoxic niche and provides a relevant technology to dissect the events involved in cancer progression.

Original languageEnglish
Article number12263
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Biomimetics
Neoplasms
Collagen
Epithelial-Mesenchymal Transition
Hypoxia
Cell Aging
Glycolysis
Cell Communication
Apoptosis
Breast Neoplasms
Technology
Growth

ASJC Scopus subject areas

  • General

Cite this

A biomimetic 3D model of hypoxia-driven cancer progression. / Liverani, Chiara; De Vita, Alessandro; Minardi, Silvia; Kang, Yibin; Mercatali, Laura; Amadori, Dino; Bongiovanni, Alberto; La Manna, Federico; Ibrahim, Toni; Tasciotti, Ennio.

In: Scientific Reports, Vol. 9, No. 1, 12263, 01.12.2019.

Research output: Contribution to journalArticle

Liverani, Chiara ; De Vita, Alessandro ; Minardi, Silvia ; Kang, Yibin ; Mercatali, Laura ; Amadori, Dino ; Bongiovanni, Alberto ; La Manna, Federico ; Ibrahim, Toni ; Tasciotti, Ennio. / A biomimetic 3D model of hypoxia-driven cancer progression. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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