Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis

e15126 Background: EL102 is a dual-action drug promoting apoptosis and inhibiting angiogenesis. It exerts its action though the inhibition of Hif1a induced hypoxic signalling and induction of the Caspase 3/7 apoptotic cascade. The drug has equal activity in normoxia and hypoxia indicating it may be equally active in these different tumor compartments. We tested its ability to circumvent chemotherapeutic drug resistance. Methods: We assessed the ability of EL102 to inhibit prostate cancer cell proliferation and motility in vitro, calculating IC50s for CWR22, 22Rv2, PC3 and DU145 prostate cancer cell lines, comparing sensitivity between androgen dependent, androgen independent and metastatic prostate cancer. Additionally we assessed the activity of EL102 in combination with docetaxel in vitro and in murine CWR22 xenografts. The ability to overcome MDR1 and BCRP mediated drug resistance was also tested using DLKP drug resistant variants which exhibit 200 fold resistance to doxorubicin, docetaxel, paclitaxel and vincristine. Results: We found that prostate cancer cell lines are sensitive to EL102 with IC50s in the region of 10-50nM. Of particular interest was the identical sensitivity of the androgen independent 22Rv1 and its androgen dependent parent CWR22, suggesting ability to overcome hormone refractory prostate cancer. Additionally we demonstrate dose response for inhibition of cell motility in metastatic DU145. In CWR22 murine mouse models treatment with EL102 resulted in decreased tumor volume compared to control. A docetaxel and EL102 combination arm demonstrated the greater inhibition of tumor growth than EL102 or docetaxel alone. The lung cancer cell line DLKP, its drug resistant variants DLKPA (MDR1 overexpressing) and DLKPMitox (BCRP overexpressing) were equally sensitive to EL102 indicating that EL102 is not a substrate for MDR1 or BCRP. Conclusions: EL102 is a potential therapeutic for the treatment of prostate cancer, in particular in combination with docetaxel, and exhbibits the potential to overcome drug resistane. Future studies will include the efficacy of this drug in prostate cancer metastatic mouse models.

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Establishment of In Vivo Ovarian Cancer Mouse Models Using Intraperitoneal Tumor Cell Injection

Methods in Molecular Biology - Ovarian Cancer ◽

10.1007/978-1-0716-1956-8_16 ◽

2021 ◽

pp. 247-254

Author(s):

Sonam Mittal ◽

Prachi Gupta ◽

Pradeep Chaluvally-Raghavan ◽

Sunila Pradeep

Keyword(s):

Ovarian Cancer ◽

Tumor Cell ◽

Mouse Models ◽

Cell Injection

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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models

Journal of Visualized Experiments ◽

10.3791/63072 ◽

2021 ◽

Author(s):

Junli Chang ◽

Fulai Zhao ◽

Xingyuan Sun ◽

Xiaoping Ma ◽

Wenlan Zhi ◽

...

Keyword(s):

Mouse Models ◽

Lung Metastasis ◽

Osteosarcoma Cell ◽

Cell Injection

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MetaTropismDB: a database of organ-specific metastasis induced by human cancer cell lines in mouse models

Database ◽

10.1093/database/baaa100 ◽

2020 ◽

Vol 2020 ◽

Author(s):

Matteo Giulietti ◽

Marco Bastianoni ◽

Monia Cecati ◽

Annamaria Ruzzo ◽

Massimo Bracci ◽

...

Keyword(s):

Mouse Models ◽

Cell Lines ◽

Cancer Cell ◽

Human Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cell Lines ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Organ Specific

Abstract The organotropism is the propensity of metastatic cancer cells to colonize preferably certain distant organs, resulting in a non-random distribution of metastases. In order to shed light on this behaviour, several studies were performed by the injection of human cancer cell lines into immunocompromised mouse models. However, the information about these experiments is spread in the literature. For each xenograft experiment reported in the literature, we annotated both the experimental conditions and outcomes, including details on inoculated human cell lines, mouse models, injection methods, sites of metastasis, organs not colonized, rate of metastasis, latency time, overall survival and the involved genes. We created MetaTropismDB, a freely available database collecting hand-curated data useful to highlight the mechanisms of organ-specific metastasis. Currently, it stores the results of 513 experiments in which injections of 219 human cell lines have been carried out in mouse models. Notably, 296 genes involved in organotropic metastases have been collected. This specialized database allows the researchers to compare the current results about organotropism and plan future experiments in order to identify which tumour molecular signatures establish if and where the metastasis will develop. Database URL: http://www.introni.it/Metastasis/metastasis.html

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Syndecan-1 facilitates breast cancer metastasis to the brain

10.1101/565648 ◽

2019 ◽

Author(s):

Megan R. Sayyad ◽

Madhavi Puchalapalli ◽

Natasha G. Vergara ◽

Sierra Mosticone Wangensteen ◽

Melvin Moore ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Brain Metastasis ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Cancer Cell Migration ◽

The Brain

AbstractPurposeAlthough survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis.MethodsTo assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 promotes brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 was silenced.ResultsSilencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that the reduction in brain metastases with Sdc1 knockdown was likely due to reduced breast cancer cell migration across the BBB and adhesion to the perivascular regions of the brain. However, there was no change in attachment to brain endothelial cells or astrocytes. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines, which may influence the BBB.ConclusionsTaken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.

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