VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche

David Lyden, et al. Nature, 438:820-827 (2005)

Speaker : 張明俐                                  Time : 2006.05.03 14:10 ~ 15:00

Commentator : 鄭宏祺 老師                 Place : Room 601

Abstract:

Many tumors have a tendency towards metastasis to specific organs. The mechanisms that determine where a primary tumor will form metastases, or why certain tumors metastasize to certain organs, are largely unknown. Some studies have implied that this preference might be caused by organ characteristics or proteins that are specific to the cell linings. The authors set up an experiment by using fluorescence labeled bone marrow derived cells and tumor cells, proving non-neoplastic cell population can portend a future metastatic site. From histological and flow cytometric studies of high metastasis-potential organs, they found that tumor cells act to set up a pre-metastatic niche ready for their arrival in the organs, by sending VEGFR1-positive haematopoietic progenitors in the beginning to create a suitable environment for them to settle in. Besides, from conditioned media assay, they also found that molecular factors secreted by the tumor cells seemed to stimulate normal fibroblast cells in the future metastatic site to produce fibronectin, which create a site for the arriving bone-marrow cells. All these findings have raised the therapeutic value of targeting VEGFR1. The inhibitors of the pathway would also be a great and potential way for metastasis blocking. This novel concept is bringing a tremendous impact on tumor staging and may alter the landscape of adjuvant chemotherapy.

References:

1. David Lyden, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature, 438:820-827 (2005)

2. Patricia S.Steeg. Emissaries set up new sites. Nature, 438:750-751 (2005)