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1.Tumour cell growth 2. Angiogenesis 3. Invasion 4. Intravasation 5. Survival in circulation 6. Extravasation Proliferation Proliferation Death dormant Single cell Death dormant Micrometastasis Clinically detectable metastasis Clinically undetectable metastasis Supplemental Figure 1. Overview of the key molecular events in metastasis. During the metastatic process, cancer cells proceed through a series of limiting steps to form a secondary tumor. In the initial stages, tumour grotwh (1) is associated with neoangiogenesis (2). Cancer cells detach from the primary tumor mass, invade adjacent tissues (3) and then enter the lymphatic or circulatory systems (4), which transport them to distant sites (5) from where they extravasate (6) and enter the surrounding microenvironment. At this point, specific factors determine whether the cells will proliferate to form a clinically detectable metastasis or if they are to remain dormant as single cells or micrometastases.
