Details

Autor(en) / Beteiligte

• Genda, Takuya
• Sakamoto, Michiie
• Ichida, Takafumi
• Asakura, Hitoshi
• Hirohashi, Setsuo

Titel

Loss of Cell-Cell Contact Is Induced by Integrin-Mediated Cell-Substratum Adhesion in Highly-Motile and Highly-Metastatic Hepatocellular Carcinoma Cells

Ist Teil von

• Laboratory investigation, 2000-03, Vol.80 (3), p.387-394

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2000

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The cadherin-mediated cell-cell adhesion system plays a critical role in normal development and morphogenesis. Inactivation of this system is thought to be responsible for cancer invasion and metastasis. A human hepatocellular carcinoma (HCC) cell line, KYN-2, was observed to have great potential for intrahepatic metastasis when orthotopically implanted into the liver of SCID mice. In vitro cultures of KYN-2 cells showed that they formed trabecular structures in suspension but lost tight cell-cell adhesion and became scattered when attached to a substratum such as collagen or fibronectin. In response to adhesion to the substratum, subcellular colocalization of E-cadherin and actin filaments were shown to be reduced, and a significant amount of α-catenin was dissociated from the E-cadherin–catenin complex in KYN-2 cells. These changes of cell-cell adhesion were blocked by inhibitory monoclonal antibodies against β1 and β5 integrins. We found that c-Src was coimmunoprecipitated with E-cadherin–catenin complex and was tyrosine-dephosphorylated and activated in the adherent cells. The tyrosine dephosphorylation of c-Src was induced by cell adhesion to the substratum and inhibited by addition of inhibitory monoclonal antibodies against β1 and β5 integrins. These findings indicate that integrin-mediated cell-substratum adhesion inhibits cadherin-mediated cell-cell adhesion, possibly through c-Src activation, and suggest that this cross-talk mediates transient inactivation of the cadherin system and plays an important role in intrahepatic metastasis of human HCC. Modulation of this interaction might provide a new approach to prevent metastasis and recurrence of HCC.