Characterization of Ovarian Cancer Stem Cell
Characterization of Ovarian Cancer Stem Cell
Specific aims: Identification and characterization of cancer stem cell-like population
 (cancer stem cells or cancer initiating cells) from primary tumor tissue, primary ascites and
 peripheral blood of ovarian cancer patients and genetically engineered mouse ovarian cancer
 cell lines.

 Objectives: In the future, individualized therapy must incorporate analysis of the cancer
 stem cells or cancer initiating cells of ovarian cancer cells when designing therapeutic
 strategies for ovarian cancer patients.

 Aims of this project:

 1. Isolation and identification of cancer stem cell-like population (cancer stem cells or
 cancer initiating cells) from primary tumor tissue, primary ascites and peripheral blood
 of ovarian cancer patients

 2. In vivo tumorigenicity assay will be performed to measure tumor formation from these
 cancer stem cell-like population when equal numbers were injected into the dorsal fat
 pad of nude mice.

 3. To establish a standard protocol of stem cell-like population maintenance

 4. Screening of potential specific biomarkers involved in these ovarian cancer stem
 cell-like population.
Ovarian cancer has the highest mortality of all gynecological cancers, with an overall 5-year
 survival rate of only 30-40%. The incidence of ovarian cancer also increased in recent year
 in Taiwan, and it became a more and more important issue. The lack of symptoms, difficulties
 in early diagnosis, insufficient accurate tumor markers, and lack of information about
 ovarian tumor biology contribute to the poor prognosis in ovarian cancer patients. The
 prognostic factors for ovarian carcinomas include tumor stage, subtype of histology, grade of
 differentiation, the residual tumor after debulking surgery, and the response to
 chemotherapy. Especially the resistance to chemotherapy plays a great role in the prognosis
 of the patients. However, the current studies present an incomplete picture of the tumor
 biology of ovarian cancer. It will be quite helpful to clinical management if the
 investigators can examine the possible underlying mechanism of tumorigenesis and drug
 resistance.

 Malignancy usually origins from the abnormal proliferate cells which accumulate several
 genetic or epigenetic aberrations. The most important key question is "What kind of cell
 could be the cancer cell?" Recent studies figure out there is "cancer-initiating cell" in the
 malignant tumor. Cancer-initiating cells organized self-renewing, anchorage-independent
 spheres and were reproducibly. Moreover, cancer-initiating cells were also capable of
 intraperitoneal tumorigenesis (demonstrating activity in their native microenvironment) and
 could serially propagate tumors in animals. Although the proportion of the cancer-initiating
 cells in the cancer tissue is very low, the characteristic abilities of cancer-initiating
 cells fulfill all currently accepted criteria for the existence of a subpopulation of
 tumor-initiating cells, and their specific detection and targeting could be highly valuable
 for therapy of tumor heterogeneity, uncontrolled proliferation, local invasion, distant
 metastasis and even resistance to current management including chemotherapy.

 Some tumor initiating cells which have the properties of cancer stem cells have been isolated
 from leukemia, breast cancer, and brain tumor. Some potential cell markers for cancer
 initiating cells were identified, including CD34(+)/CD38(+) in leukemia, CD44(+)/CD24(+) in
 breast cancer, and CD133(+)/nestin(+) in brain tumor. Aberrant cell signal transduction
 pathway of stem cell is associated with malignant transformation, such as Wnt, Hedgehog, and
 Notch pathways. Up to our knowledge, the specific antigens expressed on ovarian
 cancer-initiating cells have not been identified and characterized yet. In the current study,
 using primary human ovarian tumors, the investigators will isolate and characterized ovarian
 cancer-initiating cells fully capable of reestablishing their original tumor hierarchy in
 vivo. The investigators will also elucidate the novel diagnostic and prognostic biomarkers on
 ovarian cancer-initiating cells by identifying numerous differentially potential surface
 antigens and/or over-expressed genes. Furthermore, a mouse ovarian cancer study model will be
 genetically engineered and investigated to monitor the possible therapeutic effects of
 immunotherapy and chemotherapy to these ovarian cancer-initiating cells. The investigators
 hope to specify and to stratify the molecular patterns, response to chemotherapy, prognostic
 biomarkers in patients with ovarian cancer-initiating cells. These results might offer some
 novel ovarian cancer therapy hypothesis to evaluate its function on tumorigenesis and
 potential on targeting ovarian cancer-initiating cells.
Inclusion Criteria:

 -  Patients with ovarian carcinoma who undergo hysterectomy, bilateral oophorectomy and
 tubal resection, omentectomy, and appendectomy will be enrolled and the clinical data
 will be obtained from our hospital.