Extracellular matrix remodeling in hepatocellular carcinoma: effects of soil on seed?

Extracellular matrix plays two-edged roles, inhibitor and promoter, in the carcinogenesis and progression of hepatocellular carcinoma. On the one hand, extracellular matrix provides the survival signals, and controls the proliferation, differentiation and metastasis of hepatocellular carcinoma. On the other hand, hepatocarcinoma cells create a permissive soil by extracellular matrix remodeling, result in high proliferation, low differentiation, apoptosis block, invasion and metastasis. These malignant phenotypes are related with the change of the capsule around hepatocarcinoma cells that composed by collagens I and IV, the cell-extracellular matrix interaction induced by laminin and its receptor-integrins, and the degradation of ECM which is regulated by proteolytic enzymes and their inhibitor. Thus, normalization of ECM may represent a novel therapeutic strategy for hepatocarcinoma cells.