A Role for Epigenetic Mechanisms in Organ-Specific Breast Cancer Metastasis
Abstract
To demonstrate self-seeding., i.e., the return of circulating tumor cells to the site of origin, and investigate the mechanisms involved in this process. The dissemination of cancer cells from a primary tumor is conventionally viewed as a unidirectional process that culminates with the metastatic colonization of distant organs. 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. The tumor-derived cytokines IL-6 and IL-8 acted as CTC attractants and the poor-prognosis markers MMP1/collagenase-1 and the actin cytoskeleton component fascin-1 as mediators of CTC infiltration into mammary tumors. Self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors including, in a breast cancer model, 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2010
- Accession Number
- ADA536747
Entities
People
- Mi Y. Kim
Organizations
- Memorial Sloan Kettering Cancer Center