In vivo animal models for studying brain metastasis: value and limitations

Daphu, Inderjit; Sundstrøm, Terje; Horn, Sindre August; Huszthy, Peter C.; Niclou, Simone P.; Sakariassen, Per Øystein; Immervoll, Heike; Miletić, Hrvoje; Bjerkvig, Rolf; Thorsen, Frits

doi:10.1007/s10585-013-9566-9

Cited by 64 publications

(60 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reproducible models of brain metastasis that recapitulate the multistep process of metastases have been a major challenge for several decades (11,31,32). We have established a clinically relevant murine model of spontaneous melanoma brain metastasis in immunocompetent mice that provides a unique platform to study the pathophysiology of brain metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…One of the main challenges in studying brain metastasis is the lack of murine models that fully recapitulate invasion, migration, and distant organ colonization by tumor cells (11). We therefore set out to establish a model of spontaneous melanoma brain metastasis that will incorporate all steps of metastatic disease in immunocompetent mice.…”

Section: An Immunocompetent Mouse Model Of Spontaneous Melanoma Brainmentioning

confidence: 99%

“…Additional models were developed by injection of patient-derived melanoma cell lines, giving rise to spontaneous brain metastases in immunodeficient mice (6,7). Transgenic models of melanoma (8)(9)(10)(11)(12) are valuable for studying primary tumor initiation and progression. However, they encompass infrequent brain metastases with very long latency and thus preclude systematic analyses of the early changes in the brain microenvironment that enable metastatic growth (13).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Incipient Melanoma Brain Metastases Instigate Astrogliosis and Neuroinflammation

et al. 2016

View full text Add to dashboard Cite

Malignant melanoma is the deadliest of skin cancers. Melanoma frequently metastasizes to the brain, resulting in dismal survival. Nevertheless, mechanisms that govern early metastatic growth and the interactions of disseminated metastatic cells with the brain microenvironment are largely unknown. To study the hallmarks of brain metastatic niche formation, we established a transplantable model of spontaneous melanoma brain metastasis in immunocompetent mice and developed molecular tools for quantitative detection of brain micrometastases. Here we demonstrate that micrometastases are associated with instigation of astrogliosis, neuroinflammation, and hyperpermeability of the blood-brain barrier. Furthermore, we show a functional role for astrocytes in facilitating initial growth of melanoma cells. Our findings suggest that astrogliosis, physiologically instigated as a brain tissue damage response, is hijacked by tumor cells to support metastatic growth. Studying spontaneous melanoma brain metastasis in a clinically relevant setting is the key to developing therapeutic approaches that may prevent brain metastatic relapse.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: An Immunocompetent Mouse Model Of Spontaneous Melanoma Brainmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Incipient Melanoma Brain Metastases Instigate Astrogliosis and Neuroinflammation

et al. 2016

View full text Add to dashboard Cite

show abstract

“…By western blot analysis, we found that ZEB2 expression was decreased in brain metastatic adenocarcinoma cells, compared to their parental cell lines. Currently, there is no animal model for studying brain metastatic gastric cancer (31,32). Although we did not prepare a stable, spontaneous metastatic cell line, we were able to generate 2 'transient' brain metastatic gastric cancer cell lines by intracardiac injection.…”

Section: Increased Mirna Ratiomentioning

confidence: 94%

“…The last limitation is that the inoculation method is important in studying EMT in experimental metastasis models. The injecting of tumor cells into the bloodstream of animals is unlikely to reflect changes in epithelial and mesenchymal gene expression levels seen in primary tumors prior to the metastatic process (32).…”

Section: Increased Mirna Ratiomentioning

confidence: 99%

MicroRNA-200 family members and ZEB2 are associated with brain metastasis in gastric adenocarcinoma

Minn

Lee

Hyung

et al. 2014

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Although the incidence of brain metastasis in gastric cancer is relatively low, its prevalence may increase with improved therapy and longer survival tumors. The molecular mechanisms underlying brain metastases are not well understood. To gain insight into the mechanism of brain metastasis, we studied differences in microRNA (miRNA) expression levels in 8 cases of matched primary gastric adenocarcinoma and brain metastatic adenocarcinoma using the Illumina microRNA microarray chip. We identified 6 upregulated and 2 downregulated miRNAs in all 8 cases simultaneously. Interestingly, 2 out of 8 miRNAs (hsa-miR-141-3p and hsa-miR-200b-3p) belonged to the miR-200 family. Online microRNA database searching revealed that ZEB2 is the topranked target gene for hsa-miR141-3p and hsa-miR-200b-3p, prompting us to focus ZEB2 expression in brain metastatic adenocarcinoma. We confirmed that ZEB2 expression was markedly downregulated in some brain metastatic samples. In addition, decreased ZEB2 expression was noted by western blot analysis of 2 metastatic gastric adenocarcinoma cell types that were derived by in vivo selection following intracardiac injection of gastric cancer cell lines. In conclusion, we demonstrate that expression of miRNA-200 family members and ZEB2 are associated with brain metastases of gastric adenocarcinoma, not only in matched patient samples, but also in metastatic cell lines that were derived by in vivo selection. IntroductionAlthough the incidence of gastric cancer has been declining since 1950, gastric cancer remains the 4th most common cancer worldwide (1). The prevalence of gastric cancer shows wide geographic variations, with the highest rates found in Eastern Asia (including China, Japan and Korea), Eastern Europe, and Central and Latin America (1). In a recent report by the World Health Organization, gastric cancer was classified into 5 main types of adenocarcinomas and rare variants (2). In contrast to the better prognoses associated with early gastric cancers, advanced gastric cancers generally have poor prognoses, with known prognostic factors including stage and the number of lymph node metastases (2). Unlike lung or breast cancer, the brain metastases of gastric cancer are very rare and have been reported in <1% of clinical cases (3,4), most cases of which were reported as leptomeningeal carcinomatosis (5-7).Prolonged survival in gastric cancer patients accompanying improvements in systematic approaches and overall patient care has increased the likelihood of patients developing central nervous system metastases (8). Similarly, the incidence of brain metastasis in non-small cell lung cancer patients has increased in recent years (9), likely resulting from improved therapy, diagnostic modalities, and screening programs for early detection. In addition, evidence suggests that improved targeted therapy in patients with HER-2-positive breast cancer may increase the incidence of brain metastases (10,11). Although there is no established targeted therapy for treating gastric cancer,...

show abstract

Microinstrumentation for Brain Organoids

Patel,

Shetty,

Acha

et al. 2024

Adv Healthcare Materials

View full text Add to dashboard Cite

Brain organoids are three‐dimensional aggregates of self‐organized differentiated stem cells that mimic the structure and function of human brain regions. Organoids bridge the gaps between conventional drug screening models such as planar mammalian cell culture, animal studies, and clinical trials. They can revolutionize the fields of developmental biology, neuroscience, toxicology, and computer engineering. Conventional microinstrumentation for conventional cellular engineering, such as planar microfluidic chips; microelectrode arrays (MEAs), and optical, magnetic, and acoustic techniques, have limitations when applied to 3D organoids, primarily due to their limits with inherently 2D geometry and interfacing. Hence, there is an urgent need to develop new instrumentation that is compatible with live cell culture techniques and with scalable 3D formats of relevance to organoids. This review discusses conventional planar approaches and emerging 3D microinstrumentation necessary for advanced organoid‐machine interfaces. Specifically, the article surveys recently developed microinstrumentation, including 3D printed and curved microfluidics, 3D and fast‐scan optical techniques, buckling and self‐folding microelectrode arrays, 3D interfaces for electrochemical measurements, and 3D spatially controllable magnetic and acoustic technologies relevant to two‐way information transfer with brain organoids. The article highlights key challenges that must be addressed for robust organoid culture and reliable 3D spatiotemporal information transfer.This article is protected by copyright. All rights reserved

show abstract

In vivo animal models for studying brain metastasis: value and limitations

Cited by 64 publications

References 112 publications

Incipient Melanoma Brain Metastases Instigate Astrogliosis and Neuroinflammation

Incipient Melanoma Brain Metastases Instigate Astrogliosis and Neuroinflammation

MicroRNA-200 family members and ZEB2 are associated with brain metastasis in gastric adenocarcinoma

Microinstrumentation for Brain Organoids

Contact Info

Product

Resources

About