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.

• Authors: Mi-Young Kim, Thordur Oskarsson, Swarnali Acharyya, Don X Nguyen, Xiang H-F Zhang, Larry Norton, Joan Massagué
• Journal: Cell (Cell) Vol. 139 Issue 7 Pg. 1315-26 (Dec 24 2009) ISSN: 1097-4172 [Electronic] United States
• PMID: 20064377 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright 2009 Elsevier Inc. All rights reserved.

Chemical References

• Neoplasm Proteins

Topics

• Animals
• Breast Neoplasms (pathology)
• Humans
• Melanoma (pathology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Proteins (metabolism)
• Neoplasm Recurrence, Local
• Neoplasms (pathology, physiopathology)
• Neoplastic Cells, Circulating (pathology)
• Prognosis
• Skin Neoplasms (genetics)