Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

Fork, Melani; Escobar, Hugo Murua; Soller, Jan T.; Sterenczak, Katharina A; Willenbrock, Saskia; Winkler, Susanne; Dorsch, Martina; Reimann-Berg, Nicola; Hedrich, Hans J.; Bullerdiek, Jörn; Nolte, Ingo

doi:10.1186/1471-2407-8-240

Cited by 20 publications

(40 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with observations by Fork et al [14] no animal developed metastases which might have been caused by fast tumour progression leading to euthanasia of the animal. Moreover, there seems to be a low disposition of CT1258 cells to metastasise as the primary tumour was obtained from a 10 year old dog which -despite of several small metastases in the mesentery – showed no signs of abnormalities [13].…”

Section: Discussionsupporting

confidence: 92%

“…In conventional in vivo studies characterising tumour development in rodent models as the study by Fork et al, the tumour development was analysed via manual palpation whereby the tumours were allowed to grow to a size ranging from 5 to 8 mm which lasted 20 to 42 days after s.c. injection of CT1258 cells [14]. In the present study, the two animals inoculated with unlabeled cells showed comparable results to the Fork study.…”

Section: Discussionsupporting

confidence: 76%

“…Until now, the histological type, the karyotype and the in vivo behaviour of the CT1258 cell line, which was shown to be highly tumourigenic, were characterised [13,14]. Thereby, the induced tumours mimicked histopathologic and cytogenetic characteristics of the original tumour [14]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl2) and superparamagnetic iron oxide nanoparticles (SPIOs) in a CT1258 based in vivo model of prostate cancer

Sterenczak¹,

Meier

Glage

et al. 2012

BMC Cancer

Self Cite

View full text Add to dashboard Cite

Background Cell lines represent a key tool in cancer research allowing the generation of neoplasias which resemble initial tumours in in-vivo animal models. The characterisation of early tumour development is of major interest in order to evaluate the efficacy of therapeutic agents. Magnetic resonance imaging (MRI) based in-vivo characterisation allows visualisation and characterisation of tumour development in early stages prior to manual palpation. Contrast agents for MRI such as superparamagnetic iron oxide nanoparticles (SPIOs) and manganese chloride (MnCl2) represent powerful tools for the in-vivo characterisation of early stage tumours. In this experimental study, we labelled prostate cancer cells with MnCl2 or SPIOs in vitro and used 1 T MRI for tracing labelled cells in-vitro and 7 T MRI for tracking in an in-vivo animal model. Methods Labelling of prostate cancer cells CT1258 was established in-vitro with MnCl2 and SPIOs. In-vitro detection of labelled cells in an agar phantom was carried out through 1 T MRI while in-vivo detection was performed using 7 T MRI after subcutaneous (s.c.) injection of labelled cells into NOD-Scid mice (n = 20). The animals were scanned in regular intervals until euthanization. The respective tumour volumes were analysed and corresponding tumour masses were subjected to histologic examination. Results MnCl2 in-vitro labelling resulted in no significant metabolic effects on proliferation and cell vitality. In-vitro detection-limit accounted 105 cells for MnCl2 as well as for SPIOs labelling. In-vivo 7 T MRI scans allowed detection of 103 and 104 cells. In-vivo MnCl2 labelled cells were detectable from days 4–16 while SPIO labelling allowed detection until 4 days after s.c. injection. MnCl2 labelled cells were highly tumourigenic in NOD-Scid mice and the tumour volume development was characterised in a time dependent manner. The amount of injected cells correlated with tumour size development and disease progression. Histological analysis of the induced tumour masses demonstrated characteristic morphologies of prostate adenocarcinoma. Conclusions To the best of our knowledge, this is the first study reporting direct in-vitro MnCl2 labelling and 7 T based in-vivo MRI tracing of cancer cells in a model of prostate cancer. MnCl2 labelling was found to be suitable for in-vivo tracing allowing long detection periods. The labelled cells kept their highly tumourigenic potential in-vivo. Tumour volume development was visualised prior to manual palpation allowing tumour characterisation in early stages of the disease.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 76%

See 1 more Smart Citation

Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl2) and superparamagnetic iron oxide nanoparticles (SPIOs) in a CT1258 based in vivo model of prostate cancer

Sterenczak¹,

Meier

Glage

et al. 2012

BMC Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…In perspective, this could allow to characterise if abundantly expressed recombinant HMGA2 can increase the highly tumourigenic potential of CT1258 which was previously demonstrated in a murine NOD/SCID in vivo model [46], [47]. The first characterisation of this hypothesis needs to be carried out carefully in an intermediary in vivo mouse model.…”

Section: Discussionmentioning

confidence: 96%

Generation and Characterisation of a Canine EGFP-HMGA2 Prostate Cancer In Vitro Model

et al. 2014

Self Cite

View full text Add to dashboard Cite

The architectural transcription factor HMGA2 is abundantly expressed during embryonic development. In several malignant neoplasias including prostate cancer, high re-expression of HMGA2 is correlated with malignancy and poor prognosis. The let-7 miRNA family is described to regulate HMGA2 negatively. The balance of let-7 and HMGA2 is discussed to play a major role in tumour aetiology. To further analyse the role of HMGA2 in prostate cancer a stable and highly reproducible in vitro model system is precondition. Herein we established a canine CT1258-EGFP-HMGA2 prostate cancer cell line stably overexpressing HMGA2 linked to EGFP and in addition the reference cell line CT1258-EGFP expressing solely EGFP to exclude EGFP-induced effects. Both recombinant cell lines were characterised by fluorescence microscopy, flow cytometry and immunocytochemistry. The proliferative effect of ectopically overexpressed HMGA2 was determined via BrdU assays. Comparative karyotyping of the derived and the initial CT1258 cell lines was performed to analyse chromosome consistency. The impact of the ectopic HMGA2 expression on its regulator let-7a was analysed by quantitative real-time PCR. Fluorescence microscopy and immunocytochemistry detected successful expression of the EGFP-HMGA2 fusion protein exclusively accumulating in the nucleus. Gene expression analyses confirmed HMGA2 overexpression in CT1258-EGFP-HMGA2 in comparison to CT1258-EGFP and native cells. Significantly higher let-7a expression levels were found in CT1258-EGFP-HMGA2 and CT1258-EGFP. The BrdU assays detected an increased proliferation of CT1258-HMGA2-EGFP cells compared to CT1258-EGFP and native CT1258. The cytogenetic analyses of CT1258-EGFP and CT1258-EGFP-HMGA2 resulted in a comparable hyperdiploid karyotype as described for native CT1258 cells. To further investigate the impact of recombinant overexpressed HMGA2 on CT1258 cells, other selected targets described to underlie HMGA2 regulation were screened in addition. The new fluorescent CT1258-EGFP-HMGA2 cell line is a stable tool enabling in vitro and in vivo analyses of the HMGA2-mediated effects on cells and the development and pathogenesis of prostate cancer.

show abstract

“…Subcutaneous (s.c.) injection, which has been widely used in the development of most human tumor models (4,5), was also considered as the most appropriate method for lung cancer in our study, because orthotopic implantation is prone to complications, and its rate of tumorigenicity and metastasis formation in vivo is always unstable (6). Furthermore, unlike breast cancer and melanoma, an orthotopic model for lung cancer is relatively unavailable due to the inaccessibility of the anatomical location.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a highly metastatic model with a newly isolated lung adenocarcinoma cell line

Cui

Geng

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Lung cancer is the leading cause of malignancyrelated death worldwide, and metastasis always results in a poor prognosis. However, therapeutic progress is hampered by a deficiency of appropriate pre-clinical metastatic models. To bridge this experimental gap, we developed an in vivo metastatic model via subcutaneous (s.c.) injection. The original cell line (XL-2) adopted in this model was newly isolated from the ascites of a patient with extensive metastases of lung adenocarcinoma, thereby avoiding any alteration of its initial molecular biology features from artificial serial cultivation. After comprehensive phenotypical and histological analysis, it was identified as a lung adenocarcinoma cell line. Additionally, the drug test showed that XL-2 cell line was sensitive to docetaxel, and resistant to doxorubicin, indicating it might serve as a cell line model of drug resistance for identifying mechanisms of tumors resistant to doxorubicin. Through this s.c. model, we further obtained a highly metastatic cell line (designated XL-2sci). The metastatic rate of mice in XL-2 group was 3/10, in contrast to the rate of 9/10 in XL-2sci group. Optical imaging, micro-computed tomography (micro-CT) scanning and Transwell assays were further applied to identify the enhanced metastatic capacity of Xl-2sci cells both in vivo and in vitro. Compared with XL-2 cells, ITRAQ labeled proteomics profiling study showed that some tumor metastasisassociated proteins were upregulated in XL-2sci cells, which also indicated the reliability of our model. Proliferation ability of XL-2 and XL-2sci were also evaluated. Results showed that highly metastatic XL-2sci possessed a decreased proliferation capacity versus XL-2, which demonstrated that its increased metastatic activity was not facilitated by a faster growth rate.In conclusion, we successfully developed an in vivo metastatic model using a newly established lung adenocarcinoma cell line, which will be beneficial to further investigations of lung cancer metastasis and to the development of anti-metastasis drugs.

show abstract

Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

Cited by 20 publications

References 19 publications

Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl2) and superparamagnetic iron oxide nanoparticles (SPIOs) in a CT1258 based in vivo model of prostate cancer

Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl2) and superparamagnetic iron oxide nanoparticles (SPIOs) in a CT1258 based in vivo model of prostate cancer

Generation and Characterisation of a Canine EGFP-HMGA2 Prostate Cancer In Vitro Model

Establishment of a highly metastatic model with a newly isolated lung adenocarcinoma cell line

Contact Info

Product

Resources

About