The possible biological role of metallothionein in apoptosis.

Metallothioneins (MTs) are a family of low molecular weight proteins with a high affinity for divalent metals. Metallothionein has been shown to have a protective role in apoptosis. Specifically, it controls the cellular zinc ion levels. The proper intracellular Zn2+ level maintains the fragmentation of DNA associated with caspase-3 activity. In cancer nests, MT has been identified in the peripheral regions and associated with higher cell proliferation rates and fewer positive apoptotic cells. The expression of MT in the stroma has been linked with tumor spread. The tumor stroma may respond to tumor growth and aggressiveness by the expression of MT, thus protecting itself from and developing a resistance to apoptosis. Multistep carcinogenesis is related to a breakdown in immune response that enables tumor progression and dissemination. This breakdown is a crucial for tumor survival. The evaluation of MT expression in cancer and its stroma seems to correlate with the level of immune system inhibition in cancer-adjacent stroma.