טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentHarpaz Shlomit
SubjectBiosynthetic Material for Selective 3D Migration and
Invasion of Biopsy Explants for Cancer Cell
Characterization
DepartmentDepartment of Nanoscience and Nanotechnology
Supervisor Professor Dror Seliktar


Abstract

Cell migration is a complex process that plays an essential role in a wide variety of biological phenomena. In embryogenesis, cellular migration is an essential event in processes such as gastrulation and development of the nervous system.  Migration remains important also in the adult organism and can affect how the body responds to an infection, heals tissue injuries, maintains homeostasis, or becomes diseased with metastases, to name just a few . In metastasis, for example, tumor cells migrate from the primary site into the lymphatic and blood vessels and form new tumors in distant organs. These tumor cells are typically confined by the extracellular matrix (ECM), which is a complex 3D terrain of proteins and polysaccharides. Therefore, the ECM plays a central role in the ability of tumor cells to move and remodel their microenvironment. At the individual cell level, cells migrate and invade the ECM using either an amoeboid or a mesenchymal migration mechanism. These mechanisms are particularly important to understand to develop therapeutic strategies that can limit or dictate tumor invasion, or to design a diagnostic tool to characterize tumor cells. Because different neoplastic cell types use different migration mechanisms to invade their surrounding matrix, a material can be designed to encourage outgrowth of one cell type and block the other. We have developed a biosynthetic hybrid biomaterial, that incorporates biological macromolecules with structurally versatile synthetic polymers, to create a cross-linked network with unique properties for tumor invasion studies. It was initially implemented on artificial tumor (gel in gel construct), biopsy explants from mice (Biopsy in gel construct) to continue, and finally on biopsy explants from a human source (Biopsy in gel construct). The study validated the gel matrix composition that favours the preferential invasion and outgrowth of the tumour cells over mesenchymal cells, eliminating any unspecific migration of fibroblast or EMT effects that can alter the drug screening results. Furthermore, the anticancer drug experiments reinforced the relevance of this technique as a screening tool for chemotherapy drugs.