Title

Functional Characterization Of A Fluorescent Highly Tumorigenic Ovarian Cancer Line To Test Cellular Therapy In Experimental Models

Keywords

Cellular therapy; Cytokines; Cytoxicity; Functional characterization; Mouse model; Ovarian cancer

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 α-2b (IFNα-2b) was assayed by lactate dehydrogenase release. Sensitivity of SKOV3-AF2 cells to polyethylene glycol-IFNα-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 IFNα-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-IFNα-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. Copyright © 2011 by IGCS and ESGO.

Publication Date

4-1-2011

Publication Title

International Journal of Gynecological Cancer

Volume

21

Issue

3

Number of Pages

457-465

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1097/IGC.0b013e31820f4ef0

Socpus ID

80051647341 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/80051647341

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