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Cited by 1,339Cancer Cells and MetastasisMechanisms of cancer metastasisDevelopmental Biology and Gene Regulation

Interactions between cancer stem cells and their niche govern metastatic colonization

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Malanchi, Ilaria, Santamaria-Martínez, Albert, Susanto, Evelyn, Peng, Hong, Lehr, Hans-Anton, Delaloye, Jean-Francois, Huelsken, Joerg·2012·Nature
DOI 10.1038/nature10694
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Abstract

Metastatic growth in distant organs is the major cause of cancer mortality. The development of metastasis is a multistage process with several rate-limiting steps. Although dissemination of tumour cells seems to be an early and frequent event, the successful initiation of metastatic growth, a process termed 'metastatic colonization', is inefficient for many cancer types and is accomplished only by a minority of cancer cells that reach distant sites. Prevalent target sites are characteristic of many tumour entities, suggesting that inadequate support by distant tissues contributes to the inefficiency of the metastatic process. Here we show that a small population of cancer stem cells is critical for metastatic colonization, that is, the initial expansion of cancer cells at the secondary site, and that stromal niche signals are crucial to this expansion process. We find that periostin (POSTN), a component of the extracellular matrix, is expressed by fibroblasts in the normal tissue and in the stroma of the primary tumour. Infiltrating tumour cells need to induce stromal POSTN expression in the secondary target organ (in this case lung) to initiate colonization. POSTN is required to allow cancer stem cell maintenance, and blocking its function prevents metastasis. POSTN recruits Wnt ligands and thereby increases Wnt signalling in cancer stem cells. We suggest that the education of stromal cells by infiltrating tumour cells is an important step in metastatic colonization and that preventing de novo niche formation may be a novel strategy for the treatment of metastatic disease.

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  • De novo activation of fibroblasts at secondary sites favours establishment of macrometastases via multiple mechanisms including production of tenascin and periostin.

    “Once cancer cells have disseminated, the de novo activation of fibroblasts at secondary sites favours the establishment of macrometastases via multiple mechanisms, including the production of matrix components such as tenascin and periostin that provide supporting signals to the cancer cells94,95.”

    From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [94]

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Authors
Malanchi, I., Santamaria-Martínez, A., Susanto, E., Peng, H., Lehr, H.-A., Delaloye, J.-F., & Huelsken, J.
Affiliations
  • École Polytechnique Fédérale de Lausanne (CH)
  • Nanfang Hospital (CN)
  • Centre Hospitalier Universitaire Vaudois (CH)
Corresponding author
Huelsken, Joerg
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2011-12-07
Volume
481
Issue
7379
Pages
85-89
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature10694
OpenAlex
W2097862336
Cited by
1,339
References
0
Citations by year
2026: 32 · 2025: 35 · 2024: 57 · 2023: 81 · 2022: 89 · 2021: 140 · 2020: 83 · 2019: 100 · 2018: 93 · 2017: 98 · 2016: 117 · 2015: 108 · 2014: 117 · 2013: 106 · 2012: 77
FWCI
47.46
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • IRIS (submittedVersion)
  • Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) (submittedVersion, cc-by-nc-nd)
  • SERVAL (Université de Lausanne) (submittedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
cancer stem cells, metastatic colonization, periostin, Wnt signaling, tumor microenvironment, stromal niche, breast cancer, lung metastasis, extracellular matrix, fibroblasts, niche formation, metastasis treatment
MeSH terms
Animals, Breast Neoplasms, Female, Lung Neoplasms, Mice, Inbred C57BL, Neoplasm Metastasis, Neoplastic Stem Cells, Cell Adhesion Molecules, Stromal Cells, Mice, Stem Cell Niche, Wnt Signaling Pathway

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