A microfluidic model for researching the organ-targeted metastasis of salivary adenoid cystic carcin

来源 :第八届全国微全分析系统学术会议、第三届全国微纳尺度生物分离分析学术会议暨第五届国际微化学与微系统学术会议 | 被引量 : 0次 | 上传用户:zbwang12315
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  Objectives: Salivary Adenoid cystic carcinoma (ACC) is a common malignancy which occurs in the areas of head and neck.The growing of ACC is generally slowly,however,the rate of death is high because of its highly invasion and metastasis.Metastasis is the necessary biological process in tumor progression,it points that circulating tumor cells (CTCs) disseminate to distance targeted-organs through the blood vessels or lymphatic.Traditional metastasis models include mathematical models,animal models and in vitro models.The defects of these models have been proved that they are extremely different from in vivo human microenvironment.Microfluidic technology served as an ideal platform to construct bionic model,due to its good control in microscale.In this study,we developed a pulmonary-specific metastasis microfluidic models based on the reliable flow rate of microcirculation.Using this model,we evaluated the impact of pulmonary tissue or shear stress on the metastasis of SACC.Materials and methods: We constructed a SU-8 master by Soft lithography technique and replicated Polydimethylsiloxane (PDMS) on the mold.Two PDMS and porous polycarbonate membrane were sealed by cured in a 80℃ oven for 30mins.Two cell lines were used in our study,including Human umbilical vein endothelial cell line (HUVEC) and the high metastatic ACC cell line ACC-M.Primary pulmonary cells were isolated from SD male rat.The expression of vimentin and pan cytokeratin is used to identify the types of primary cells.Results: The microfluidic device was consisted of two PDMS layers,sandwiching a thin and porous polycarbonate membrane.The porous membrane between the top and bottom channel was seeded with HUVECs as endothelial barrier.The top channel was used to mimic blood vessels containing circulating ACC-M by a syringe pump according to the blood flow velocity of microcirculation in vivo.To mimic the target organs,primary cells from lung were seeded in the bottom channel.CXCL12 in the bottom channel was used as positive control.Cell culture medium without CXCL12 or cells was used as negative control.It was found that the primary pulmonary cells and CXCL12 attracted significantly greater number of ACC-M cells than negative control.In addition,shear stress and endothelial barrier integrity affect tumor cell adhesion.Conclusions: We developed a microfluidic device to model organ-targeted metastasis of tumor.We investigated lung-target metastasis of ACC.Our results proved that this device is an ideal model to study tumor metastasis.We hope the model would be a useful platform for study the mechanism of tumor metastasis and anti-metastasis drug screening.
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