Journal Article DKFZ-2020-00450

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A Perivascular Niche in the Bone Marrow Hosts Quiescent and Proliferating Tumorigenic Colorectal Cancer Cells.

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2020
Wiley-Liss Bognor Regis

International journal of cancer 147(2), 519-531 () [10.1002/ijc.32933]
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Abstract: Disseminated tumor cells (dTCs) can frequently be detected in the bone marrow (BM) of colorectal cancer (CRC) patients, raising the possibility that the BM serves as a reservoir for metastatic tumor cells. Identification of dTCs in BM aspirates harbors the potential of assessing therapeutic outcome and directing therapy intensity with limited risk and effort. Still, the functional and prognostic relevance of dTCs is not fully established. We have previously shown that CRC cell clones can be traced to the bone marrow (BM) of mice carrying patient-derived xenografts. However, cellular interactions, proliferative state and tumorigenicity of dTCs remain largely unknown. Here, we applied a co-culture system modeling the microvascular niche and used immunofluorescence imaging of the murine BM to show that primary CRC cells migrate towards endothelial tubes. dTCs in the BM were rare, but detectable in mice with xenografts from most patient samples (8/10) predominantly at perivascular sites. Comparable to primary tumors, a substantial fraction of proliferating dTCs were detected in the BM. However, most dTCs were found as isolated cells, indicating that dividing dTCs rather separate than aggregate to metastatic clones - a phenomenon frequently observed in the microvascular niche model. Clonal tracking identified subsets of self-renewing tumor-initiating cells in the BM that formed tumors out of BM transplants, including one subset that did not drive primary tumor growth. Our results indicate an important role of the perivascular BM niche for CRC cell dissemination and show that dTCs can be a potential source for tumor relapse and tumor heterogeneity. This article is protected by copyright. All rights reserved.

Classification:

Note: 2020 Jul 15;147(2):519-531 / #EA:B280#LA:B280#

Contributing Institute(s):
  1. B280 Translationale funktionelle Krebsgenomik (B280)
  2. C060 Biostatistik (C060)
  3. Lichtmikroskopie (W210)
  4. DKTK DD zentral (DD01)
Research Program(s):
  1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020
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Medline ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2020-02-24, last modified 2024-02-29



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