Phd Degree / Doktora

Permanent URI for this collectionhttps://hdl.handle.net/11147/2869

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Subject: search.filters.subject.MetastasisWoS Q: search.filters.wosQuartile.N/A

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  • Doctoral Thesis
    Detection of the Metastatic Potential of Breast Cancer Cell Lines To Specific Target Tissues
    (01. Izmir Institute of Technology, 2021) Fıratlıgil Yıldırır, Burcu; Yalçın Özuysal, Özden
    Breast cancer is one of the most frequently diagnosed cancer types and the second leading cause of cancer-associated deaths in women. Breast cancer begins as a local disease which can then metastasize to distant sites specifically to bone, lung and liver. The increasing rate of the metastasis-related deaths asserts the need to develop in vitro diagnostic strategies representing in vivo properties better. In this study, two different lab-on-a-chip (LOC) platforms, IC- and EX-chips, were used to detect the invasion and extravasation potentials, respectively, of breast cancer cells to 3D in vitro generated bone, lung, liver and breast microenvironments. The metastatic MDAMB231, but not non-metastatic MCF7 breast cancer cells showed higher invasion and extravasation potentials towards lung and liver microenvironments than breast microenvironment. Lung-specific but not bone-specific metastatic subclonal cells invaded significantly towards lung microenvironment. On the other hand, an intensive invasion was observed in bone-specific but not lung-specific metastatic subclonal cells towards bone microenvironment demonstrating different in vivo metastatic behaviors of breast cancer cells. Overall, the tissue-specific invasion and extravasation capacities of breast cancer cells were demonstrated with IC- and EX-chips where the physiologically more relevant bone, lung, liver and breast homing target sites were generated by a specific emphasis on ECM components, stromal cells and secreted factors. This study is important in providing a basis for the development of diagnostic tools and precision therapeutics for breast cancer metastasis.
  • Doctoral Thesis
    Engineering Target Tissue in Lab-On Devices for Predicting Homing Choices of Metastatic Cancer
    (Izmir Institute of Technology, 2020) Batı Ayaz, Gizem; Pesen Okvur, Devrim; Yavuz, Oktay
    The metastatic cascade of cancer results in the extravasation of the tumor to other parts of the body. Metastasis is the leading cause of cancer related deaths. Breast cancer is the most common cancer in women, and lung is one of the organs with the most metastasis. For this reason, it is critical to engineer a tissue microenvironment that includes complex cell-cell interactions with co-culture of endothelial, epithelial and stromal cells, and the invasion and extravasation steps of metastasis can be observed for early diagnosis of metastasis. Vascularization is the critical step for engineering the tissues. The in vitro models used today are insufficient to create the tissue environment closest to in vivo conditions. Recently developed lab-on-a-chip platforms provide suitable environments for mimicking the in vivo structure in tissue engineering studies. In this research: -Different lab-on-a-chip devices fabricated to engineer breast and lung target tissues. -For the first time, epithelial, fibroblast and endothelial cells were tri-cultured and breast and lung tissue environments were engineering with microvasculature. -Different gel, media and cell numbers have been optimized for engineering of breast and lung tissue environments with microvascularization. -Different matrix environments have been optimized to observe invasion and/or extravasation steps separately or together.