טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentKatz Ehood
SubjectIsolation and Characterization of Ovarian Cancer Cells
Derived from Ascites Fluid
DepartmentDepartment of Medicine
Supervisors Professor Karl Skorecki
Dr. Maty Zukerman
Full Thesis textFull thesis text - English Version


Abstract

In recent years the concept by which the surrounding tissue microenvironment contributes to cancer progression, has slowly become an accepted theory. To further examine this theory, our lab has developed a novel experimental system in which undifferentiated human Embryonic Stem Cells (hESC) are injected into the hind limb musculature of severe combined immunodeficient (SCID) mice, proliferate and differentiate into derivatives of all three embryonic germ layers, thereby generating a hESC-derived cellular microenvironment called teratoma.

Injection of established cancer cell lines into the teratoma tissue, demonstrates the following findings: a) Observation of growth of tumor cells with high proliferative capacity within the teratoma tissue. b) Identification of invasion of tumor cells into surrounding differentiated teratoma tissues and structures. c) Identification of blood vessels of human origin, growing adjacent to and within the cancer cells-derived tumor. To this end, this novel experimental system has been suggested to be used as a pre-clinical platform for investigating and manipulating the stromal response in tumor cell growth as an additional tool in cancer research.

The existence of different cell sub-populations in breast cancer and brain tumor masses reveals a hierarchical paradigm in which these cell sub-populations exhibit different tumorigenic properties, such as proliferative capacity, invasiveness and metastatic capacity. Identification of different subgroups of cells with different tumorigenic properties, can contribute to better understanding of the casual steps leading to tumor formation and its organization in a solid state at the molecular level.

The aim of this project is to identify different cell sub-populations freshly harvested from ovarian cancer patient ascites fluid and to characterize them in terms of proliferative capacity, invasiveness and metastatic capacity in a murine tissue microenvironment (direct xenograft model) versus a hESC-derived cellular microenvironment as described in the above experimental model.

Seven different cell sub-populations have been isolated and characterized, each showing different morphological characteristics, proliferation capacity, intensity of surface antigens appearance and above all, different tumorigenic capacities.

A striking observation was that certain cancer cell sub-populations which did not develop into tumors in a conventional murine xenograft model did generate tumors in a hESC-derived cellular microenvironment. These results suggest that the hESC-derived cellular microenvironment has the additional experimental advantage of the capability to unveil certain cancer cell subpopulations that do not grow into a tumor in direct tumor xenograft and most probably are not accessible to testing of anticancer therapies used in the conventional model.