A role of angiogenesis in cancer metastasis - Cloning and characterization of genes associated with invasion-independent metastasis-

点击翻译按钮获取中文摘要

It is generally believed that active invasion by cancer cells is essential to the metastatic process. In this report, we describe a murine mammary tumor (MCH66) model of metastasis that does hot require invasion into the vascular wall of the target organ, in this case, the lung. The process involves intravasation of tumor nests surrounded by sinusoidal blood vessels, followed by intravascular tumor growth in the lung, without penetration of the vascular wall during the process. Comparative studies using a non-metastatic MCH66 clone (MCH66C8) and another highly invasive metastatic cell line (MCH416) suggested that high angiogenic activity and sinusoidal remodeling of tumor blood vessels wereprerequisites for MCH66 metastasis. Differential CDNA analysis identified several genes that were over-expressed by MCH66, including genes for the angiogenesis factor pleiotrophin, and ECM-associated molecules that may modulate the microenvironment towards neovascularization. Our analyses suggest that tumor angiogenesis plays a role in the induction of invasion-independent metastasis.Of the invasion-independent metastasis-associated gene candidates cloned as above, Pleiotrophin (PTN), Secretory leukocyte protease inhibitor (SLPI), Fibulin-5, Insulin-like growth factor-binding protein-5 (IGFBP5), LPS-binding protein (LPSBP), Cellular retinol binding protein-1 (CRBP1) were transfected in MCH66C8 and MCH416. Transfectants of PTN (C8-PTN or 416-PTN) did not facilitate lung metastasis or develop sinusoidal vasculature. Induction of invasion-independent metastasis by other 5 genes were under investigation at presentThis model should prove useful in screening and development of new therapeutic agents for cancer metastasis.