Abstract 1402: ADAM9 involved in the regulation of integrin-dependent and -independent migration and invasion behavior of cancer cells
Authors: Liu Jer-Ming , He Yun-Chi , Shen Chia-Ning , Sung Shian-Ying 
Published: June 2012

A disintegrin and metalloproteinase (ADAM) superfamily, has been demonstrated involved in tumor progression and metastasis. Previously, Fritzsche et al., performed the clinic evaluation of ADAM9 expression and indicated the correlation between ADAM9 expression and poor prognosis of prostate cancer patients. Josson et al., further demonstrated the increased of therapeutic effect by combination of ADAM9 knockdown and radiation/chemotherapy of prostate cancer cells. Preliminary study by us revealed decreased of cancer extravasation and metastasis in ADAM9 knockdown strain by in vivo intra-cardiac injection. These data suggests dual biological role of ADAM9 in cancer cells, i.e., increased stress resistance and involved in metastasis regulation. To further elucidate the role of ADAM9 in cancer metastasis and stress response, cross-linking and pull-down assay was performed. LC-MS/MS analyses of proteins demonstrated highly interaction of ADAM9 with plectin, which can be confirmed by immunoprecipitation analyses. Plectin is a scaffold protein which bind to intergin beta4 and maintain the structure of hemidesmosome to regulate cell adhesion and migration. We sugess that ADAM9 involve in hemidesmosome turnover and cancer cell metastasis potential. This make cancer cell to adapt the environment change and escape from adverse circumstances. To further evaluate the role of ADAM9 in cell migration and invasion that may associated with plectin, 3D culture of cells in collagen or matrigel and time-lapse microscopic analyses of cell invasion ability was performed. Interestingly, we observed faster but shorter movement and amoebae-like structure during our 36 hours monitoring invasion behavior in cancer cell knockdown of ADAM9. In contrast, parental cells showed long distance extrusion and migration and long spindle like structure during the invasion. This may reflect the difference during cancer metastasis behaviors, in which parental cells showed mesenchymal-like invasion and switched to amoebae-like invasion after knockdown of ADAM9. It has been showed the mesenchymal invasion involved integrin and release of MMPs in order to digest the matrices. Therefore, 3D matrigel mixed with proteinase inhibitors and invasion assay was performed. We noticed the parental cell switching to amoebae-like activities and shorter movement just like our ADAM9 knockdown strain in protease inhibitor matrigel. In conclusions, we observed the switching between mesenchymal-like invasion and amoebae-like activities in prostate cancer cells. We further noticed that interaction of ADAM9 with hemidesmosome compartment, plectin, play the critical role in this processing. This interaction with plectin and integrin beta4 may indicated that ADAM9 play a role in maintain cancer mesenchyma-like activities during metastasis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1402. doi:10.1158/1538-7445.AM2011-1402