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Tumor Self-Seeding by Circulating Cancer Cells
Open accessAbstract
Cancer cells that leave the primary tumor can seed metastases in distant organs, and it is thought that this is a unidirectional process. Here we show that circulating tumor cells (CTCs) can also colonize their tumors of origin, in a process that we call "tumor self-seeding." Self-seeding of breast cancer, colon cancer, and melanoma tumors in mice is preferentially mediated by aggressive CTCs, including those with bone, lung, or brain-metastatic tropism. We find that the tumor-derived cytokines IL-6 and IL-8 act as CTC attractants whereas MMP1/collagenase-1 and the actin cytoskeleton component fascin-1 are mediators of CTC infiltration into mammary tumors. We show that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors including the chemokine CXCL1. Tumor self-seeding could explain the relationships between anaplasia, tumor size, vascularity and prognosis, and local recurrence seeded by disseminated cells following ostensibly complete tumor excision.
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“Consequently, tumor self-seeding leads to enhanced angiogenesis, tumor growth, stromal recruitment through seed-derived factors including the chemokine CXCL1, anaplasia, tumor size, and vascularity.”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [147]
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“Mechanistically, tumors secrete IL-6 and IL-8 cytokines to attract CTC”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [147]
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“In this way, aggressive CTCs preferentially mediate self-seeding of breast, melanoma, and colon cancers in mice, including those with bone, brain, or lung -metastatic tropism.”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [147]
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“Even more interesting is that, in contrast to the traditional view that tumor cell metastases occur unidirectional, the reverse process is also possible through CTC-mediated “self-seeding”.”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [147]
The cited source says what the claim attributes to it.
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“while CTC infiltration into mammary tumors is mediated by MMP1/collagenase-1 and the actin cytoskeleton component fascin-1.”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [147]
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“Finally, there is the prognosis for local recurrence by seeding of disseminated cells after apparently complete tumor ablation [147, 148].”
From Tumor microenvironment complexity and therapeutic implications at a glance (2020) · cites this paper as [147]
In the citing paper
“CXCL1 emerged among a set of genes whose expression is associated with lung relapse in breast tumors, including tumors that had not been exposed to prior chemotherapy (Minn et al., 2007; Minn et al., 2005), and as a gene that increases the aggressiveness of circulating breast tumor cells (Kim et al., 2009).”
From A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis (2012) · cites this paper as Kim et al., 2009
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Metadata
- Authors
- Kim, M.-Y., Oskarsson, T., Acharyya, S., Nguyen, D. X., Zhang, X. H.-F., Norton, L., & Massagué, J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Massagué, Joan
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 139
- Issue
- 7
- Pages
- 1315-1326
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2810531
- OpenAlex
- W2152393981
- Cited by
- 1,335
- References
- 57
- Citations by year
- 2026: 16 · 2025: 44 · 2024: 61 · 2023: 90 · 2022: 89 · 2021: 88 · 2020: 96 · 2019: 87 · 2018: 68 · 2017: 82 · 2016: 91 · 2015: 96 · 2014: 102 · 2013: 82 · 2012: 98
- FWCI
- 40.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- Howard Hughes Medical Institute
- National Institutes of Health
- National Cancer Institute (P01CA094060, CA94060, P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- circulating tumor cells, breast cancer, colon cancer, melanoma, interleukin-6, interleukin-8, MMP-1, fascin, CXCL1, tumor angiogenesis, tumor growth, local recurrence, metastatic tropism, actin cytoskeleton
- MeSH terms
- Animals, Breast Neoplasms, Humans, Melanoma, Mice, Inbred BALB C, Neoplastic Cells, Circulating, Neoplasm Proteins, Neoplasm Recurrence, Local, Neoplasms, Prognosis, Skin Neoplasms, Mice
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