{"alternative_title":["ISTA Thesis"],"title":"Role of microenvironment heterogeneity in cancer cell invasion","status":"public","related_material":{"record":[{"relation":"part_of_dissertation","id":"679","status":"public"},{"relation":"part_of_dissertation","id":"10703","status":"public"},{"status":"public","id":"7885","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","id":"9429","status":"public"}]},"publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","oa":1,"date_created":"2023-01-26T11:55:16Z","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","department":[{"_id":"GradSch"},{"_id":"MiSi"}],"abstract":[{"text":"Detachment of the cancer cells from the bulk of the tumor is the first step of metastasis, which\r\nis the primary cause of cancer related deaths. It is unclear, which factors contribute to this step.\r\nRecent studies indicate a crucial role of the tumor microenvironment in malignant\r\ntransformation and metastasis. Studying cancer cell invasion and detachments quantitatively in\r\nthe context of its physiological microenvironment is technically challenging. Especially, precise\r\ncontrol of microenvironmental properties in vivo is currently not possible. Here, I studied the\r\nrole of microenvironment geometry in the invasion and detachment of cancer cells from the\r\nbulk with a simplistic and reductionist approach. In this approach, I engineered microfluidic\r\ndevices to mimic a pseudo 3D extracellular matrix environment, where I was able to\r\nquantitatively tune the geometrical configuration of the microenvironment and follow tumor\r\ncells with fluorescence live imaging. To aid quantitative analysis I developed a widely applicable\r\nsoftware application to automatically analyze and visualize particle tracking data.\r\nQuantitative analysis of tumor cell invasion in isotropic and anisotropic microenvironments\r\nshowed that heterogeneity in the microenvironment promotes faster invasion and more\r\nfrequent detachment of cells. These observations correlated with overall higher speed of cells at\r\nthe edge of the bulk of the cells. In heterogeneous microenvironments cells preferentially\r\npassed through larger pores, thus invading areas of least resistance and generating finger-like\r\ninvasive structures. The detachments occurred mostly at the tips of these structures.\r\nTo investigate the potential mechanism, we established a two dimensional model to simulate\r\nactive Brownian particles representing the cell nuclei dynamics. These simulations backed our in\r\nvitro observations without the need of precise fitting the simulation parameters. Our model\r\nsuggests the importance of the pore heterogeneity in the direction perpendicular to the\r\norientation of bias field (lateral heterogeneity), which causes the interface roughening.","lang":"eng"}],"publication_status":"published","date_published":"2022-12-22T00:00:00Z","supervisor":[{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K"}],"article_processing_charge":"No","month":"12","date_updated":"2024-09-10T12:04:26Z","type":"dissertation","file":[{"file_id":"12402","date_created":"2023-01-26T11:58:14Z","file_size":42059787,"date_updated":"2023-12-21T23:30:03Z","content_type":"application/pdf","access_level":"open_access","creator":"cchlebak","embargo":"2023-12-20","file_name":"PhD-Thesis_Saren Tasciyan_formatted_aftercrash_fixed_600dpi_95pc_final_PDFA3b.pdf","checksum":"cc4a2b4a7e3c4ee8ef7f2dbf909b12bd","relation":"main_file"},{"date_updated":"2023-12-21T23:30:03Z","file_id":"12403","file_size":261256696,"date_created":"2023-01-26T12:00:10Z","checksum":"f1b4ca98b8ab0cb043b1830971e9bd9c","relation":"source_file","content_type":"application/x-zip-compressed","embargo_to":"open_access","creator":"cchlebak","access_level":"closed","file_name":"Source Files - Saren Tasciyan - PhD Thesis.zip"}],"degree_awarded":"PhD","day":"22","ddc":["610"],"file_date_updated":"2023-12-21T23:30:03Z","year":"2022","_id":"12401","language":[{"iso":"eng"}],"citation":{"ieee":"S. Tasciyan, “Role of microenvironment heterogeneity in cancer cell invasion,” Institute of Science and Technology Austria, 2022.","mla":"Tasciyan, Saren. <i>Role of Microenvironment Heterogeneity in Cancer Cell Invasion</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:12401\">10.15479/at:ista:12401</a>.","short":"S. Tasciyan, Role of Microenvironment Heterogeneity in Cancer Cell Invasion, Institute of Science and Technology Austria, 2022.","chicago":"Tasciyan, Saren. “Role of Microenvironment Heterogeneity in Cancer Cell Invasion.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:12401\">https://doi.org/10.15479/at:ista:12401</a>.","ista":"Tasciyan S. 2022. Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria.","apa":"Tasciyan, S. (2022). <i>Role of microenvironment heterogeneity in cancer cell invasion</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12401\">https://doi.org/10.15479/at:ista:12401</a>","ama":"Tasciyan S. Role of microenvironment heterogeneity in cancer cell invasion. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:12401\">10.15479/at:ista:12401</a>"},"publication_identifier":{"issn":["2663-337X"]},"has_accepted_license":"1","author":[{"last_name":"Tasciyan","first_name":"Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X"}],"page":"105","doi":"10.15479/at:ista:12401"}