Cited by 125Cellular Mechanics and InteractionsHydrogels: synthesis, properties, applications3D Printing in Biomedical Research

Recapitulating the human tumor microenvironment: Colon tumor-derived extracellular matrix promotes angiogenesis and tumor cell growth

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Romero-López, Mónica, Trinh, Andrew L., Sobrino, Agua, Hatch, Michaela M.S., Keating, Mark T., Fimbres, Cristhian, Lewis, David E., Gershon, Paul D. +4 more·2017·Biomaterials

Abstract

Extracellular matrix (ECM) is an essential and dynamic component of all tissues and directly affects cellular behavior by providing both mechanical and biochemical signaling cues. Changes in ECM can alter tissue homeostasis, potentially leading to promotion of cellular transformation and the generation of tumors. Therefore, understanding ECM compositional changes during cancer progression is vital to the development of targeted treatments. Previous efforts to reproduce the native 3D cellular microenvironment have utilized protein gels and scaffolds that incompletely recapitulate the complexity of native tissues. Here, we address this problem by extracting and comparing ECM from normal human colon and colon tumor that had metastasized to liver. We found differences in protein composition and stiffness, and observed significant differences in vascular network formation and tumor growth in each of the reconstituted matrices, both in vitro and in vivo. We studied free/bound ratios of NADH in the tumor and endothelial cells using Fluorescence Lifetime Imaging Microscopy as a surrogate for the metabolic state of the cells. We observed that cells seeded in tumor ECM had higher relative levels of free NADH, consistent with a higher glycolytic rate, than those seeded in normal ECM. These results demonstrate that the ECM plays an important role in the growth of cancer cells and their associated vasculature.

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Crossref · 10.1016/j.biomaterials.2016.11.034

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  • Complex components of the tumor microenvironment can significantly affect the growth and metastasis of cancer via mechanical and biochemical factors.

    “Various studies have demonstrated that complex components can significantly affect the growth and metastasis of cancer via mechanical and biochemical factors113–116.”

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  1. [59]Serebriiskii I Castelló-Cros R Lamb A Golemis EA Cukierman E Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells Matrix Biology 2008 27 573 585 18411046 PMC2603546

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Authors
Romero-López, M., Trinh, A. L., Sobrino, A., Hatch, M. M. S., Keating, M. T., Fimbres, C., Lewis, D. E., Gershon, P. D., Botvinick, E. L., Digman, M., Lowengrub, J. S., & Hughes, C. C. W.
Affiliations
University of California, Irvine (US)
Corresponding author
Hughes, Christopher C.W.
Venue
Biomaterials
Publisher
Elsevier BV
Published
2017-02
Volume
116
Pages
118-129
ISSN
0142-9612 (ISSN-L)
OpenAlex
W2550719584
Cited by
125
References
64
Citations by year
2026: 5 · 2025: 11 · 2024: 20 · 2023: 15 · 2022: 16 · 2021: 16 · 2020: 14 · 2019: 9 · 2018: 8 · 2017: 11
FWCI
6.41
Type
journal article
Language
en
Open access
Locations
  • Biomaterials (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (NIH UH3 TR00048, R01HL60067)
  • CCWH (NIH SIG 1S10OD016328)
  • PDG (NIH P41-RRO3155)
  • MD (NIH EB015890, NIH R01HL085339)
  • ELB and MTK
  • National Science Foundation (DGE-1144901)
  • Chao Family Comprehensive Cancer Center
  • National Cancer Institute Center (P30A062203)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
extracellular matrix, colon cancer, tumor microenvironment, angiogenesis, liver metastasis, extracellular matrix stiffness, vascular network formation, tumor growth, NADH fluorescence lifetime, glycolysis, endothelial cells, cancer metabolism
MeSH terms
Colonic Neoplasms, Extracellular Matrix, Humans, Neovascularization, Pathologic, Tumor Cells, Cultured, Cell Proliferation, Tumor Microenvironment

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