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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Tumor self-seeding leads to enhanced angiogenesis, tumor growth, stromal recruitment through seed-derived factors including CXCL1, anaplasia, tumor size, and vascularity.
“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]
The Abstract and Discussion report that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment; the Results identify seeder-derived CXCL1 as contributing to stromal recruitment. But the Discussion presents links to anaplasia, tumor size, and vascularity as possible explanations for clinical associations, not as established outcomes of self-seeding. Page numbers are not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTumors secrete IL-6 and IL-8 cytokines to attract CTCs.
“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]
Experimental — accuracy not yet measuredAggressive CTCs preferentially mediate self-seeding of breast, melanoma, and colon cancers in mice, including those with bone, brain, or lung metastatic tropism.
“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]
In contrast to the traditional view that tumor cell metastases occur unidirectionally, the reverse process is also possible through CTC-mediated self-seeding.
“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]
CTC infiltration into mammary tumors is mediated by MMP1/collagenase-1 and the actin cytoskeleton component fascin-1.
“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]
There is a prognosis for local recurrence by seeding of disseminated cells after apparently complete tumor ablation.
“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]
CXCL1 expression is associated with lung relapse in breast tumors, including tumors not exposed to prior chemotherapy, and increases aggressiveness of circulating breast tumor cells.
“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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- 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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