1. Shedding of a cell froma primary tumor to colonize distant site.
2. Travels via blood or lymphatic vasculature to distant site.
3. Colonization occurs when cell becomes lodged in, or extravasates from, vasculature.
Protease involve the process in Metastasis
1. Attached to invasive cell surface.
2. Activates tissue plasminogen to plasmin, which is not specific.
3. Tissue remodeling.
4. Degrades MMP framents.
Treatment of cancers with protease inhibitors, e.g. Serine protease inhibitors (Serpins) or Tissue Inhibitors of Metalloproteinases (TIMPs), is moderately effective in inhibiting metastasis. MarimistatR and BAY12-9566R are recent examples. Multiple proteases are secreted by metastatic cancer cells and thus, specific inhibition of only one system is ineffective in arresting the whole process.