Tumor self-seeding by circulating cancer cells

Kim et al.  Cell 139, 1315–26, 2009

Speaker: Shuo-Fu Lin (林碩甫)                                            Time: 15:10~16:00, Apr. 14, 2009

Commentator: Dr. Bei-Chang Yang (楊倍昌 老師)             Place: Room 601

Abstract

The progression of cancer includes primary tumor growth and secondary metastasis. In order to gain space and growth factor, tumor cells at the primary sites could enter the systemic circulation and spread to distant organs [1].Even surgical removal of the primary tumor, the tumor might relapse again. In order to illustrate the relationship between the large tumor size, poor prognosis and local relapse, the authors establish a hypothesis about “self-seeding”, a phenomenon that circulating cancer cells (CTCs) can reinflatrate into their original tumor site [2]. To test the hypothesis, the authors set up a new tumor-seeding assay based on mouse tumor xenograft model. Within the same mouse, the authors inject GFP-luc-labeled tumor cells and tumor cells that carry no label at opposite locations, and found that labeled tumor cells can disseminated into the non-labeled tumor on opposite site, regardless of the site of injection, whether is at the mammary fat pad, under the skin, or intravenously. The authors also show that highly metastatic derivatives, retrieved from the original metastasized tumor, readily infiltrate into pre-existing tumors but not to the mammary glands. Further analysis of the gene expression pattern, the authors identified four factors that are responsible for executing these functions: cytokines IL-6 and IL-8, which attracts the most aggressive segment of the circulating tumor cell population, MMP1/collagenase-1 and the actin cytoskeleton component fascin-1, which mediates the infiltration of circulating tumor cells into a tumor. They also showed that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors like the chemokine CXCL1. In conclusion, the circulating cancer cells can reinfi­ltrate into tumors at their site of origin to promote the growth of the primary tumors. These results give us opportunities to explore a new target therapy that may interfere with the self-seeding process and even prevent tumor progression.

References

1.      Chambers,  A.F.,  Groom,  A.C.,  and  MacDonald, I.C. (2002) Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2: 563–572.

2.      Norton L. & Massagué J. (2008) Is cancer a disease of self-seeding? Nat.Med. 12: 875-878