4. Hrvatski kongres kliniËke citologije 4th Croatian Congress ... - Penta
4. Hrvatski kongres kliniËke citologije 4th Croatian Congress ... - Penta
4. Hrvatski kongres kliniËke citologije 4th Croatian Congress ... - Penta
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Clinical Cytology - Oral Presentations<br />
DEDIFFERENTIATION THERAPY AND DARWINISM FOR SORTING OF OVARIAN<br />
CANCER STEM CELLS<br />
Tomuleasa C1 , Soritãu O1 , Ciucã DR2 , Susman S2 , Mihu C2 1Ion Chiricuta Oncology Institute, Department of Cancer Immunology, Cluj Napoca, Romania<br />
2Iuliu Hatieganu University of Medicine and Pharmacy, Department of Pathology, Cluj<br />
Napoca, Romania<br />
Introduction. The cellular mechanisms underlying the increasing aggressiveness associated<br />
with ovarian cancer progression are poorly understood. Coupled with a lack of<br />
identification of specific markers that could aid early diagnoses, the disease becomes<br />
a major cause of cancer-related mortality in women. The high incidence of recurrence<br />
attributable to multidrug resistance and the multiple histologic phenotypes indicative<br />
of multipotency suggest a stem-like etiology of ovarian cancer. Here we adopted suspension<br />
culture combined with anti-cancer regimens as a strategy for screening ovarian<br />
cancer stem cells. These tumor stem cells could survive and be highly enriched in<br />
non-adherent suspension culture while chemotherapeutic agents could destroy most<br />
rapidly dividing cancer cells and spare relatively quiescent cancer stem cells. Material<br />
and Methods. MLS human ovarian cancer cells were cultured in serum-free medium,<br />
suplemented with Epidermal Growth Factor, basic Fibroblast Growth Factor, B27 and<br />
N2. Cells of passage 8 were treated in combination with anticancer agents Doxorubicin<br />
and Carboplatin at different peak plasma concentrations for 24 hours, and then maintained<br />
under suspension culture. The stem-like properties were confirmed by immunocytochemistry<br />
staining techniques, by multidrug resistance assays and by their ability<br />
to grow in an anchorage-independent manner in vitro as spheroids. Selected cells were<br />
also injected subcutaneously into CD1 mice to observe tumour formation. Results and<br />
Discussion.Here we present direct evidence that the aggressiveness of human ovarian<br />
cancer may be a result of transformation and dysfunction of stem cells in the ovary.<br />
The tumorigenic clones, even on serial transplantation continue to establish tumours,<br />
theraby confirming their identity as tumor stem cells. Suspension culture combined with<br />
anticancer regimens provides an effective means of isolating, culturing and purifying<br />
ovarian cancer stem cells.<br />
ciprian_tomuleasa@yahoo.com<br />
111<br />
4 th <strong>Croatian</strong> <strong>Congress</strong> of Clinical Cytology / 1 st <strong>Croatian</strong> Symposium of Analytical Cytology / 2 nd <strong>Croatian</strong> Symposium of Cytotechnology