Bioluminescence imaging for in vivo monitoring of local recurrence mesothelioma model

Shi, Yandong; Hollenstein, Andreas; Felley‐Bosco, Emanuela; Fraefel, Cornel; Ackermann, Matthias; Soltermann, Alex; Weder, Walter; Stahel, Rolf A.; Pruschy, Martin; Opitz, Isabelle

doi:10.1016/j.lungcan.2010.12.020

Cited by 4 publications

(11 citation statements)

References 7 publications

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“…We first established that the tumors arising from the parental chemo-naïve II-45 cells showed sarcomatoid morphology with pleomorphic features and only focal areas of epithelioid appearance (classified by pathologist S.K.) consistent with previous reports16. We next examined the tumors from the chemo-resistant cell lines and found that these demonstrated different morphologies ranging from epithelioid in the gemcitabine resistant tumors (GemR) to almost exclusively sarcomatoid in the PemR and ComboR tumors (Figure 4A).…”

Section: Resultssupporting

confidence: 74%

“…Since its development in 198715, the syngeneic II-45 rat mesothelioma cell line, also referred to as IL-4516, has been accepted and utilized as a relevant model system for pleural mesothelioma research17181920. This model exhibits an essentially sarcomatoid morphology16.…”

mentioning

confidence: 99%

“…This model exhibits an essentially sarcomatoid morphology16. While sarcomatoid mesothelioma accounts for only 10–15% of all diagnosed cases, it is more aggressive and less responsive to treatment21 resulting in decreased survival22.…”

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confidence: 99%

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Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma

Hudson

Weir

Moon

et al. 2014

Sci Rep

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Mesothelioma is inherently chemo-resistant with only 50% of patients responding to the standard of care treatments, and consequently it has a very grim prognosis. The aim of this study was to establish a panel of chemo-resistant mesothelioma models with clinically relevant levels of resistance as tools for investigating chemo-resistance and identifying new treatments for mesothelioma. Chemo-resistant cell lines were established in vitro and characterized in vivo using syngeneic Fischer rats. Tumors derived from all chemo-resistant cell lines were immunohistochemically classified as mesothelioma. Homozygous deletion of p16INK4A/p14ARF and increased expression of several ATP-binding cassette transporters were demonstrated, consistent with findings in human mesothelioma. Further, the acquisition of chemo-resistance in vitro resulted in changes to tumor morphology and overall survival. In conclusion, these models display many features corresponding with the human disease, and provide the first series of matched parental and chemo-resistant models for in vitro and in vivo mesothelioma studies.

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Section: Resultssupporting

confidence: 74%

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confidence: 99%

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Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma

Hudson

Weir

Moon

et al. 2014

Sci Rep

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“…To investigate the role of Hh signaling in MPM stroma, we employed our previously described rat MPM model, generated by the implantation of a rat mesothelioma cell line, IL45-luc, underneath parietal pleura of immunocompetent rats (19). IL45-luc cells cultured in vitro in the presence of 10% FBS expressed high levels of Gli1, Ptch1, and Smo, however, mRNA levels of all Hh ligands were very low or undetectable.…”

Section: Resultsmentioning

confidence: 99%

“…IL45-expressing luciferase (IL45-luc) was generated by us in 2011 by stable transfection of IL45 with luciferase-expressing vector (19). Both IL45 and IL45-luc were maintained in RPMI1640 containing 1 mmol/L sodium pyruvate, penicillin/streptomycin (P/S), 200 mg/mL Geneticin (G418), and 10% FBS at 37 C with 5% CO 2 .…”

Section: Cell Culturementioning

confidence: 99%

Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma

Meerang

Bérard

Felley-Bosco

et al. 2016

Molecular Cancer Therapeutics

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An autocrine-driven upregulation of the Hedgehog (Hh) signaling pathway has been described in malignant pleural mesothelioma (MPM), in which the ligand, desert Hh (DHH), was produced from tumor cells. However, our investigation revealed that the Hh pathway is activated in both tumor and stroma of MPM tumor specimens and an orthotopic immunocompetent rat MPM model. This was demonstrated by positive immunohistochemical staining of Glioma-associated oncogene 1 (GLI1) and Patched1 (PTCH1) in both tumor and stromal fractions. DHH was predominantly expressed in the tumor fractions. To further investigate the role of the Hh pathway in MPM stroma, we antagonized Hh signaling in the rat model of MPM using a Hh antagonist, vismodegib, (100 mg/kg orally). Daily treatment with vismodegib efficiently downregulated Hh target genes Gli1, Hedgehog Interacting Protein (Hhip), and Ptch1, and caused a significant reduction of tumor volume and tumor growth delay. Immunohistochemical analyses revealed that vismodegib treatment primarily downregulated GLI1 and HHIP in the stromal compartment along with a reduced expression of previously described fibroblast Hh-responsive genes such as Fibronectin (Fn1) and Vegfa. Primary cells isolated from the rat model cultured in 3% O 2 continued to express Dhh but did not respond to vismodegib in vitro. However, culture supernatant from these cells stimulated Gli1, Ptch1, and Fn1 expression in mouse embryonic fibroblasts, which was suppressed by vismodegib. Our study provides new evidence regarding the role of Hh signaling in MPM stroma in the maintenance of tumor growth, emphasizing Hh signaling as a treatment target for MPM. Mol Cancer Ther; 15(5); 1095-105. Ó2016 AACR.

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Evaluation of imaging techniques for the assessment of tumour progression in an orthotopic rat model of malignant pleural mesothelioma†

Meerang

Boss

Kenkel

et al. 2014

European Journal of Cardio-Thoracic Surgery

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Bioluminescence imaging for in vivo monitoring of local recurrence mesothelioma model

Cited by 4 publications

References 7 publications

Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma

Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma

Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma

Evaluation of imaging techniques for the assessment of tumour progression in an orthotopic rat model of malignant pleural mesothelioma†

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