Functional Characterization of a Fluorescent Highly Tumorigenic Ovarian Cancer Line to Test Cellular Therapy in Experimental Models

    Authors

    S. B. Ingersoll; S. Ahmad; G. P. Stoltzfus; S. Patel; M. J. Radi; N. J. Finkler; J. R. Edwards;R. W. Holloway

    Comments

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    Abbreviated Journal Title

    Int. J. Gynecol. Cancer

    Keywords

    Ovarian cancer; Cellular therapy; Mouse model; Cytokines; Cytoxicity; Functional characterization; HIGH-DOSE INTERLEUKIN-2; BREAST-CANCER; INTRAPERITONEAL CISPLATIN; DENDRITIC CELLS; CYTO-TOXICITY; KILLER-CELLS; STAGE-III; PHASE-II; T-CELLS; PACLITAXEL; Oncology; Obstetrics & Gynecology

    Abstract

    Objectives: The objective of this study was to functionally characterize a fluorescent highly tumorigenic ovarian cancer line to test cellular therapy in combination with cytokines or chemotherapies in experimental models. Methods: A fluorescent highly tumorigenic subline (SKOV3-AF2) was derived from the SKOV3 ovarian cancer cell line. Peripheral blood mononuclear cell (PBMC)-mediated cytotoxicity of SKOV3-AF2 in the presence of interleukin 2 (IL-2) and interferon alpha-2b (IFN alpha-2b) was assayed by lactate dehydrogenase release. Sensitivity of SKOV3-AF2 cells to polyethylene glycol-IFN alpha-2b and IL-2 was assayed in a xenograph nude mouse model. Histopathology was performed to determine necrosis and tumor-infiltrating lymphocytes in the solid tumors. Reverse transcriptase-polymerase chain reaction was used for gene expression analyses of E-cadherin and cysteine-rich 61 (CCN1). Results: The SKOV3-AF2 subline exhibits increased cytotoxicity (up to 70%), mediated by PBMCs, IL-2, and IFN alpha-2b, compared with parental SKOV3-red fluorescent protein (RFP) cells. SKOV3-AF2 cells are more tumorigenic in vivo as indicated by tumor incidence, time to sacrifice, tumor weight, and ascitic fluid production. SKOV3-AF2 tumor growth was inhibited by polyethylene glycol-IFN alpha-2b but not low-dose IL-2. Histopathology revealed that the tumors consisted of poorly differentiated surface epithelial carcinoma. SKOV3-RFP, and -AF2 cell lines as well as -AF2 tumors expressed E-cadherin. SKOV3-AF2 derived tumors expressed CCN1; however, the SKOV3-RFP and SKOV3-AF2 cell lines did not. Conclusions: Characterization of SKOV3-AF2 cells revealed that it is more susceptible to PBMC-mediated cytotoxicity than SKOV3-RFP and highly tumorigenic in a xenograph model, and AF-2 tumors express genes that promote aggressive behavior. Collectively, our data suggest that the SKOV3-AF2 subline will be a useful tool to test cellular therapy for the treatment of ovarian cancer utilizing experimental models.

    Journal Title

    International Journal of Gynecological Cancer

    Volume

    21

    Issue/Number

    3

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    457

    Last Page

    465

    WOS Identifier

    WOS:000288743700007

    ISSN

    1048-891X

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