Oral Presentation 14th International Biennial Conference on Metastasis Research 2012

Innate immune system mediates focal metastasis (#15)

Sachie Hiratsuka-Nakamura 1
  1. Tokyo Women's Medical University, Tokyo, Japan

Distant metastatic process includes a cascade of sequential events, including tumor cell intravasation at the primary site, tumor cell circulation, homing to distant organs, extravasation into these organs, and subsequent colonization, growth and angiogenesis. The “premetastatic phase” describes a period during which a distant organ is rendered more hospitable towards circulating tumor cells with metastatic potential, facilitated by the presence of a distant primary tumor. Primary tumor-derived factors, such as cytokines, chemokines, amine oxidases and exsozome, can modify the lung environment before tumor cell arrival. Spontaneous lung metastasis often presents as a discrete series of lesions separated by large areas of unaffected lung tissue. Last year, I showed that primary tumors induce distinct foci of vascular hyperpermeability in premetastatic lung, which co-localize with increased tumor cell homing. Endothelial cell-specific, inducible FAK-knockdown suppresses hyperpermeability and reduces tumor cell homing to these foci. This year, we show that innate immune system is involved in the generation of focal permeability regions in premetastatic lungs, and contributes focal metastases.