**2.3 Endothelial attachment and extravasation of cancer cells**

Needless to say, tumor angiogenesis as well as lymphatic vessel formation are important for delivery of cancer cells from the primary tumor to secondary organs. HGF enhances angiogenesis via induction of the proliferation and morphogenesis of endothelial cells (EC) (Bussolino *et al*., 1992; Nakamura *et al*., 1996). Actually, HGF supplementation leads to the enhancement of tumor angiogenesis *in vivo* (Laterra *et al*., 1997). Recent studies delineated the capacity of HGF to induce lymphatic morphogenesis (Kajiya *et al*., 2005; Saito *et al*., 2006). Thus, HGF is considered to facilitate cancer metastasis via neo-induction of vascular or lymphatic vessel beds. HGF has a direct effect on EC for enhancing tight adhesion of tumor cells on endothelium via FAK phosphorylation (Kubota *et al*., 2009a). Furthermore, HGF decreases endothelial occludin, a cell-cell adhesion molecule (Jiang *et al*., 1999a). Under such a loss of EC-EC integrity, HGF decreases the trans-endothelial resistance of tumor vessels and enhances cancer invasion across an EC barrier (*i.e.,* intravasation in primary tumors and extravasation in metastatic organs) (**Fig. 1**).
