Inhibition of Tissue Invasion and Metastasis

The defining event of a malignancy is the ability of rogue cells to advance from the primary tumor, invade adjacent tissue, and travel to distant sites to found new colonies. Most cancer mortality is due to these distant metastases, which arise as amalgams of cancer cells and normal cells recruited from the host tissue. The mechanisms whereby tumor cells can undergo invasion and metastasis are complex and are still being defined. However, to elicit these migrations of cancer cells, it is clear that molecules involved in interactions between cells and between cells and their matrix must be involved. These proteins include the cell adhesion molecules (CAMs), which are members of the immunoglobulin and calcium-dependent cadherin families, and integrins, which link cells to their extracellular matrix. The most commonly observed altered protein is E-cadherin, which is normally expressed ubiquitously in epithelial cells, mediating cell-to-cell interactions; loss of cadherin is associated with metastasis in a majority of epithelial cancers. In addition, extracellular proteases, including the matrix metalloprotein-ases (MMPs) are upregulated, while protease inhibitors are downregulated in the metastatic process.26

As outlined above, green tea and EGCG are effective antiangiogenic agents. They also are found to inhibit genes related to adhesion, invasion, and metastasis, including urokinase, MMP-2, and MMP-9.4748 Interestingly, when black tea and a soy phytochemical concentrate were combined in a mouse model of orthotopic androgen-sensitive human prostate cancer, the combination resulted in a syner-gistic interaction to inhibit prostate tumorigenicity, final tumor weight, and metastases to lymph nodes in vivo.49

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