Transcriptome analysis of novel B16 melanoma metastatic variants generated by serial intracarotid artery injection.

Transcriptome analysis of novel B16 melanoma metastatic variants generated by serial intracarotid artery injection.

Publication date: Jan 16, 2025

The incidence of brain metastases (BrM) in patients with metastatic melanoma is reported to be 30-50% and constitutes the third most frequent BrM after breast and renal cancers. Treatment strategies including surgical resection, stereotactic radiation, and immunotherapy have improved clinical response rates and overall survival, but the changes that occur in circulating melanoma cells to promote invasion of the brain are not fully understood. To investigate brain tropism, we generated new variants of the B16 mouse melanoma model by serially passaging B16 cells through the brain of immune competent syngeneic C57BL/6 mice. Cells were injected into the right carotid artery and recovered from the brain after the mice had reached the study endpoint due to tumor burden, then expanded in vitro and reinjected. We compared the transcriptomes of 4th generation B16 cell populations from separate lineages with the founder B16-F0 cells. Gene set enrichment analysis (GSEA) of differentially expressed protein coding genes revealed that cells isolated from the brain as well as from the lung and meninges expressed higher levels of genes associated with an epithelial to mesenchymal transition (EMT), upregulation of the KRAS signaling pathway, and a metastasis aggressiveness gene signature associated with poor survival in melanoma patients. Principal component analysis of differentially expressed genes showed that 4th generation melanoma cells isolated from the brain, lung and meninges from one lineage were distinct from those of the other three lineages. Among the differentially expressed genes, transcript levels of several genes, including Itgb2, Rftn2, and Kcnn4, were significantly higher in all cell populations that comprised this lineage compared with all cell populations from the other three lineages. In conclusion, we have derived an aggressive, highly brain metastatic B16 variant associated with leptomeningeal disease by serially passaging cells in vivo.

Open Access PDF

Concepts Keywords
Competent Animals
Kcnn4 B16-F0
Mice Brain metastasis
Principal Brain Neoplasms
Tumor Carotid Arteries
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Female
Gene Expression Profiling
Leptomeningeal disease
Lipid rafts
Melanoma
Melanoma, Experimental
Mice
Transcriptome

Semantics

Type Source Name
disease MESH B16 melanoma
disease MESH brain metastases
disease MESH melanoma
pathway KEGG Melanoma
disease MESH renal cancers
disease MESH tumor
disease MESH metastasis
drug DRUGBANK Coenzyme M
pathway REACTOME Reproduction
disease MESH hemorrhage
drug DRUGBANK Ketamine
drug DRUGBANK Xylazine
drug DRUGBANK Povidone-iodine
drug DRUGBANK Ethanol
drug DRUGBANK Sulodexide
drug DRUGBANK Isoflurane
pathway REACTOME Digestion
drug DRUGBANK Ademetionine
drug DRUGBANK Honey
pathway REACTOME Extracellular matrix organization
drug DRUGBANK Huperzine B
disease MESH noma
drug DRUGBANK L-Phenylalanine
drug DRUGBANK Pentaerythritol tetranitrate
pathway REACTOME Nervous system development
drug DRUGBANK Hyaluronic acid
drug DRUGBANK Pidolic Acid
disease MESH carcinoma
disease MESH renal carcinoma
drug DRUGBANK Cholesterol
pathway REACTOME Translation
drug DRUGBANK Calcium
disease MESH death
drug DRUGBANK L-Valine
disease MESH tics
drug DRUGBANK Esomeprazole
drug DRUGBANK Trestolone
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH hepatocellular carcinoma
pathway KEGG Hepatocellular carcinoma
disease MESH recurrence
disease MESH fibrosarcoma
drug DRUGBANK Erlotinib

Original Article

(Visited 2 times, 1 visits today)

Leave a Comment

Your email address will not be published. Required fields are marked *