Invasion and metastasis are complex processes involving multiple discrete steps; they begin with local tissue invasion, followed byinfiltration of nearby blood and lymphatic vessels by cancer cells.Malignant cells are eventually transpoed through haematogenousand lymphatic spread to distant sites within the body, where theyform micrometastases that will eventually grow into macroscopicmetastatic lesions Cadherin-1 (CDH1) is a calcium-dependent cell-cell adhesionglycoprotein that facilitates assembly of organised cell sheets intissues, and increased expression is recognised as an antagonistof invasion and metastasis. In situ tumours usually retain CDH1production, whereas loss of CDH1 production due to down-regulation or occasional mutational inactivation of CDH1 hasbeen observed in human cancers, suppoing the theory thatCDH1 plays a key role in suppression of invasion and metastasis.Cross-talk between cancer cells and cells of the surroundingstromal tissue is involved in the acquired capability for invasivegrowth and metastasis. Mesenchymal stem cells in tumourstroma have been found to secrete CCL5, a protein chemokinethat helps recruit leucocytes into inflammatory sites. With thehelp of paicular T-cell-derived cytokines (interleukin (IL)-2and interferon-gamma (IFN-g)), CCL5 induces proliferation andactivation of natural killer cells and then acts reciprocally oncancer cells to stimulate invasive behaviour. Macrophages atthe tumour periphery can foster local invasion by supplyingmatrix-degrading enzymes such as metalloproteinases andcysteine cathepsin proteases.The lungs, liver, brain, and bones are the most common metastasis locations from solid tumors. Ref Harrison 20th edition pg 580