A perivascular niche in the bone marrow hosts quiescent and proliferating tumorigenic colorectal cancer cells.
Animals
Bone Marrow
/ metabolism
Cell Tracking
Coculture Techniques
Colorectal Neoplasms
/ metabolism
Green Fluorescent Proteins
/ genetics
Human Umbilical Vein Endothelial Cells
Humans
Mesenchymal Stem Cells
/ cytology
Mice
Neoplastic Cells, Circulating
/ metabolism
Optical Imaging
Prognosis
Stem Cell Niche
Time-Lapse Imaging
Tumor Cells, Cultured
/ cytology
Xenograft Model Antitumor Assays
bone marrow niche
colorectal cancer
disseminated tumor cells
metastasis formation
patient-derived xenograft
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
received:
06
11
2019
revised:
31
01
2020
accepted:
05
02
2020
pubmed:
23
2
2020
medline:
9
3
2021
entrez:
21
2
2020
Statut:
ppublish
Résumé
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 BM of mice carrying patient-derived xenografts. However, cellular interactions, proliferative state and tumorigenicity of dTCs remain largely unknown. Here, we applied a coculture system modeling the microvascular niche and used immunofluorescence imaging of the murine BM to show that primary CRC cells migrate toward 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 was 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.
Substances chimiques
Green Fluorescent Proteins
147336-22-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
519-531Informations de copyright
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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