期刊
CELL
卷 139, 期 7, 页码 1315-1326出版社
CELL PRESS
DOI: 10.1016/j.cell.2009.11.025
关键词
-
资金
- National Institutes of Health [CA94060]
- Hearst Foundation
- Alan and Sandra Gerry Metastasis Research Initiative
- Department of Defense Era of Hope postdoctoral fellowship
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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