Authors: | Kim, M. Y.; Oskarsson, T.; Acharyya, S.; Nguyen, D. X.; Zhang, X. H. F.; Norton, L.; Massague, J. |
Article Title: | Tumor Self-Seeding by Circulating Cancer Cells |
Abstract: | 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. © 2009 Elsevier Inc. All rights reserved. |
Keywords: | signal transduction; controlled study; unclassified drug; human cell; cancer recurrence; nonhuman; neoplasms; animal cell; mouse; animals; mice; actin; animal tissue; mus; melanoma; metastasis; neoplasm recurrence, local; skin neoplasms; tumor volume; interleukin 8; neoplasm proteins; breast neoplasms; mice, inbred balb c; neoplastic cells, circulating; colon cancer; nucleotide sequence; breast tumor; cancer cell; cancer infiltration; interleukin 6; tumor growth; stroma cell; tumor vascularization; interstitial collagenase; cytoskeleton; collagenase; tumor embolism; anaplastic carcinoma; humdisease; collagenase 1; cxcl1 chemokine; fascin; fascin 1; tumor seeding |
Journal Title: | Cell |
Volume: | 139 |
Issue: | 7 |
ISSN: | 0092-8674 |
Publisher: | Cell Press |
Date Published: | 2009-12-24 |
Start Page: | 1315 |
End Page: | 1326 |
Language: | English |
DOI: | 10.1016/j.cell.2009.11.025 |
PUBMED: | 20064377 |
PROVIDER: | scopus |
PMCID: | PMC2810531 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 20" - "Export Date: 30 November 2010" - "CODEN: CELLB" - "Source: Scopus" |