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The molecular biology of brain metastasis.

ABSTRACT: Metastasis to the central nervous system (CNS) remains a major cause of morbidity and mortality in patients with systemic cancers. Various crucial interactions between the brain environment and tumor cells take place during the development of the cancer at its new location. The rapid expansion in molecular biology and genetics has advanced our knowledge of the underlying mechanisms involved, from invasion to final colonization of new organ tissues. Understanding the various events occurring at each stage should enable targeted drug delivery and individualized treatments for patients, with better outcomes and fewer side effects. This paper summarizes the principal molecular and genetic mechanisms that underlie the development of brain metastasis (BrM).

SUBMITTER: Rahmathulla G

PROVIDER: S-EPMC3317231 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The molecular biology of brain metastasis.

Rahmathulla Gazanfar G Toms Steven A SA Weil Robert J RJ

Journal of oncology 20120308

Metastasis to the central nervous system (CNS) remains a major cause of morbidity and mortality in patients with systemic cancers. Various crucial interactions between the brain environment and tumor cells take place during the development of the cancer at its new location. The rapid expansion in molecular biology and genetics has advanced our knowledge of the underlying mechanisms involved, from invasion to final colonization of new organ tissues. Understanding the various events occurring at e ...[more]

PMID: 22481931

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Project description:We established a model of human melanoma metastasis to identify differentially expressed genes in brain metastasis, compared to cutaneous melanoma from which they were developed. Such genes may control brain metastasis. The identification and characterization of these genes would advance the understanding of the metastatic process and may lead to new diagnostics and therapeutic approach. Brain metastases occur in almost 40% of melanoma patients. The median survival of such patients does not exceed a few months. Very little information is available on mechanisms underlying the progression of melanoma towards brain metastasis. The function, and significance of the various factors involved in melanoma progression must be deciphered using relevant models. Currently, most human melanoma brain metastasis models consist of xenografted cells inoculated into immune-deficient mice mainly by intracarotid or intra-cardiac administration. We generated a reproducible melanoma brain metastasis model, consisting of brain-metastasizing variants and local, sub-dermal variants that originate from the same melanomas thus sharing a common genetic background. The brain metastasizing variants were obtained by intra-cardiac inoculation. One of the brain metastasizing variants when inoculated sub-dermally yielded spontaneous brain dormant micrometastasis. Cells from the spontaneous brain micrometastasis when removed from the brain microenvironment proliferate very well in vitro and generate tumors in the skin being the orthotopic organ site. The brain metastasis and micro-metastasis cells expressed higher levels of ANGPTL4, COX-2, MMP1, MMP2 and PRAME and lower levels of CLDN1, CYR61 and IL-6R than the cutaneous variants. These gene products may be involved in melanoma brain metastasis and may serve as novel brain metastasis biomarkers and targets for therapy. 8 Samples (arrays) were analyzed. We generated pairwise comparisons between cutaneous and brain metastatic variants of the same genetic background, using Partek Genomics Suite, in the three melanoma models. Genes with p≤5% and a fold-change difference of ≥1.25 or <-1.25 were selected.

Dataset Information

The molecular biology of brain metastasis.

Publications

The molecular biology of brain metastasis.

Similar Datasets

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