Mucinous adenocarcinoma developed from human fallopian tube epithelial cells through defined genetic modifications

Shan, Weiwei; Mercado‐Uribe, Imelda; Zhang, Jing; Rosen, Daniel; Wei, Jian‐Jun; Liu, Jinsong

doi:10.4161/cc.20544

Cited by 38 publications

(40 citation statements)

References 23 publications

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“…OVCAR5 and OVCAR3 were identical at the cellular and tumor level for p53 and WT1 expression. OVCAR8 expressed WT1 mostly in the nucleolar compartment, which has previously been described in mucinous tumors [22]. Only three of the models tested here in vivo (COV362, OVCAR3, and CAOV3) were also screened for chemotherapy sensitivity in vitro [16].…”

Section: Discussionmentioning

confidence: 99%

In vivo tumor growth of high-grade serous ovarian cancer cell lines

Mitra

Davis

Tomar

et al. 2015

Gynecologic Oncology

168

154

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Objective Genomic studies of ovarian cancer (OC) cell lines frequently used in research revealed that these cells do not fully represent high-grade serous ovarian cancer (HGSOC), the most common OC histologic type. However, OC lines that appear to genomically resemble HGSOC have not been extensively used and their growth characteristics in murine xenografts are essentially unknown. Methods To better understand growth patterns and characteristics of HGSOC cell lines in vivo, CAOV3, COV362, KURAMOCHI, NIH-OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVSAHO, OVKATE, SNU119, UWB1.289 cells were assessed for tumor formation in nude mice. Cells were injected intraperitoneally (i.p.) or subcutaneously (s.c.) in female athymic nude mice and allowed to grow (maximum of 90 days) and tumor formation was analyzed. All tumors were sectioned and assessed using H&E staining and immunohistochemistry for p53, PAX8 and WT1 expression. Results Six lines (OVCAR3, OVCAR4, OVCAR5, OVCAR8, CAOV3, and OVSAHO) formed i.p xenografts with HGSOC histology. OVKATE and COV362 formed s.c. tumors only. Rapid tumor formation was observed for OVCAR3, OVCAR5 and OVCAR8, but only OVCAR8 reliably formed ascites. Tumors derived from OVCAR3, OVCAR4, and OVKATE displayed papillary features. Of the 11 lines examined, three (Kuramochi, SNU119 and UWB1.289) were non-tumorigenic. Conclusions Our findings help further define which HGSOC cell models reliably generate tumors and/or ascites, critical information for preclinical drug development, validating in vitro findings, imaging and prevention studies by the OC research community.

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Section: Discussionmentioning

confidence: 99%

In vivo tumor growth of high-grade serous ovarian cancer cell lines

Mitra

Davis

Tomar

et al. 2015

Gynecologic Oncology

168

154

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“…Although cell culture is a valuable model and allows for continual passage of human FTE and for targeted genetic manipulation, traditional two-dimensional culture is unable to simulate interaction with the fallopian stroma and generally does not allow for maintenance of ciliated FTE [6–8]. Although an advanced FTE model, which retains ciliated cells has been reported, this model manipulates the architecture and eliminates the stromal cells [9].…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional modeling of the human fallopian tube fimbriae

Eddie

Quartuccio

Zhu

et al. 2015

Gynecologic Oncology

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Objective Ovarian cancer is the most lethal gynecological malignancy that affects women. Recent data suggests the disease may originate in the fallopian fimbriae; however, the anatomical origin of ovarian carcinogenesis remains unclear. This is largely driven by our lack of knowledge regarding the structure and function of normal fimbriae and the relative paucity of models that accurately recapitulate the in vivo fallopian tube. Therefore, a human three-dimensional (3D) culture system was developed to examine the role of the fallopian fimbriae in serous tumorigenesis. Methods Alginate matrix was utilized to support human fallopian fimbriae ex vivo. Fimbriae were cultured with factors hypothesized to contribute to carcinogenesis, namely; H2O2 (1mM) a mimetic of oxidative stress, insulin (5 µg/ml) to stimulate glycolysis, and estradiol (E2, 10nM) which peaks before ovulation. Cultures were evaluated for changes in proliferation and p53 expression, criteria utilized to identify potential precursor lesions. Further, secretory factors were assessed after treatment with E2 to identify if steroid signaling induces a pro-tumorigenic microenvironment. Results 3D fimbriae cultures maintained normal tissue architecture up to 7 days, retaining both epithelial subtypes. Treatment of cultures with H2O2 or insulin significantly induced proliferation. However, p53 stabilization was unaffected by any particular treatment, although was induced by ex vivo culturing. Moreover, E2-alone treatment significantly induced its canonical target PR and expression of IL8, a factor linked to poor outcome. Conclusions 3D alginate cultures of human fallopian fimbriae provide an important microphysicological model, which can be further utilized to investigate serous tumorigenesis originating from the fallopian tube.

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“…We found that expression of expression of Sp1 and hCtr1 is increased in the oncogenic Ras-transformed, SV40 T/t and telomerase reverse transcriptase-immortalized human fallopian tube epithelial (FTE) cells. FTE has been suggested as origin of ovarian cancers [87]. Furthermore, expression of hCtr1 and Sp1 can be induced in Kras-transformed FTE by Cu chelation but not in the non-transformed immortalized FTE cells cannot (L.Y., J. L, MTK, unpublished results).…”

Section: The Sensing Mechanisms Of Cu Bioavailability By Sp1mentioning

confidence: 84%

Targeting drug transport mechanisms for improving platinum-based cancer chemotherapy

Chen

Liang

et al. 2015

Expert Opinion on Therapeutic Targets

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Introduction Platinum (Pt)-based antitumor agents remain important chemotherapeutic agents for treating many human malignancies. Elevated expression of the human high-affinity copper transporter 1 (hCtr1), resulting in enhanced Pt drug transport into cells, has been shown to be associated with improved treatment efficacy. Thus, targeting hCtr1 upregulation is an attractive strategy for improving the treatment efficacy of Pt-based cancer chemotherapy. Area covered Regulation of hCtr1 expression by cellular copper homeostasis is discussed. Association of elevated hCtr1 expression with intrinsic sensitivity of ovarian cancer to Pt drugs is presented. Mechanism of copper-lowering agents in enhancing hCtr1-mediated cis-diamminedichloroplatinum (II) (cisplatin, cDDP) transport is reviewed. Applications of copper chelation strategy in overcoming cDDP resistance through enhanced hCtr1 expression are evaluated. Expert opinion While both transcriptional and posttranslational mechanisms of hCtr1 regulation by cellular copper bioavailability have been proposed, detailed molecular insights into hCtr1 regulation by copper homeostasis remain needed. Recent clinical study using a copper-lowering agent in enhancing hCtr1-mediated drug transport has achieved incremental improvement in overcoming Pt drug resistance. Further improvements in identifying predictive measures in the subpopulation of patients that can benefit from the treatment are needed.

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Mucinous adenocarcinoma developed from human fallopian tube epithelial cells through defined genetic modifications

Cited by 38 publications

References 23 publications

In vivo tumor growth of high-grade serous ovarian cancer cell lines

In vivo tumor growth of high-grade serous ovarian cancer cell lines

Three-dimensional modeling of the human fallopian tube fimbriae

Targeting drug transport mechanisms for improving platinum-based cancer chemotherapy

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