Abstract
During the metastatic process tumor cells circulate in the blood stream and are carried to various organs. In order to spread to different organs tumor cell—endothelial cell interactions are crucial for extravasation mechanisms. It remains unclear if tumor cell dissemination to the spinal bone occurs by passive entrapment of circulating tumor cells or by active cellular mechanisms mediated by cell surface molecules or secreted factors. We investigated the seeding of three different tumor cell lines (melanoma, lung and prostate carcinoma) to the microvasculature of different organs. Their dissemination was compared to biologically passive microbeads. The spine and other organs were resected three hours after intraarterial injection of tumor cells or microbeads. Ex vivo homogenization and fluorescence analysis allowed quantification of tumor cells or microbeads in different organs. Interestingly, tumor cell distribution to the spinal bone was comparable to dissemination of microbeads independent of the tumor cell type (melanoma: 5.646% ± 7.614%, lung: 6.007% ± 1.785%, prostate: 3.469% ± 0.602%, 7 μm beads: 9.884% ± 7.379%, 16 μm beads: 7.23% ± 1.488%). Tumor cell seeding differed significantly between tumor cells and microbeads in all soft tissue organs. Moreover, there were significant differences between the different tumor cell lines in their dissemination behaviour to soft tissue organs only. These findings demonstrate that metastatic dissemination of tumor cells to spinal bone and other osseous organs is mediated by passive entrapment of tumor cells similar to passive plugging of microvasculature observed after intraarterial microbeads injection.
Highlights
Increasing incidence of spinal bone metastasis leading to epidural spinal cord compression and devastating neurological deficits is becoming a major clinical challenge for neurooncologicalPLOS ONE | DOI:10.1371/journal.pone.0162540 September 7, 2016Cell versus Microsphere DisseminationProgram funded by the Volkswagen Foundation and the Charité Foundation
We demonstrate that metastatic tumor cell seeding to the spine and other osseous organs is primarily driven by passive entrapment as the distribution is comparable between tumor cells and microbeads
Tumor cell seeding in soft tissue organs is shown to depend on tumor cell type and the corresponding homing organ indicating an active, biologically triggered mechanism
Summary
Increasing incidence of spinal bone metastasis leading to epidural spinal cord compression and devastating neurological deficits is becoming a major clinical challenge for neurooncologicalPLOS ONE | DOI:10.1371/journal.pone.0162540 September 7, 2016Cell versus Microsphere DisseminationProgram funded by the Volkswagen Foundation and the Charité Foundation. The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication
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