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Analysis of tumor- and stroma-supplied proteolytic networks in different metastatic tumor microenvironments identifies a critical role for cathepsin S in brain metastasis

ABSTRACT: Metastasis is a multistage process that requires cancer cells to escape from the primary tumor, survive in the circulation, seed at distant sites and colonize these foreign tissue environments. Each of these processes involves rate-limiting steps that are influenced by stromal cells of the tumor microenvironment. While the tumor microenvironment has emerged as a major regulator of cancer progression in other organ sites, our knowledge of the brain metastatic microenvironment is currently very limited. Thus, we aim to dissect signatures of tumor-stroma interactions in brain metastasis in order to identify factors that regulate the homing, seeding and outgrowth of cancer cells in this highly specialized microenvironment. We took advantage of an experimental metastasis model in which variants of the human breast cancer line MDA-MB-231 home to the brain in xenografted animals. To simultaneously capture gene expression changes in the tumor and stromal compartment, we used a dual species-specific microarray platform, the HuMuProtIn array, to discriminate between differentially expressed protease or protease inhibitor genes of human (tumor) or murine (stromal) origin.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE47930 | GEO | 2014/07/04

SECONDARY ACCESSION(S): PRJNA208376

REPOSITORIES: GEO

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Analysis of tumor- and stroma-supplied proteolytic networks in different metastatic tumor microenvironments identifies a critical role for cathepsin S in brain metastasis

Project description:Metastasis is a multistage process that requires cancer cells to escape from the primary tumor, survive in the circulation, seed at distant sites and colonize these foreign tissue environments. Each of these processes involves rate-limiting steps that are influenced by stromal cells of the tumor microenvironment. While the tumor microenvironment has emerged as a major regulator of cancer progression in other organ sites, our knowledge of the brain metastatic microenvironment is currently very limited. Thus, we aim to dissect signatures of tumor-stroma interactions in brain metastasis in order to identify factors that regulate the homing, seeding and outgrowth of cancer cells in this highly specialized microenvironment. We took advantage of an experimental metastasis model in which variants of the human breast cancer line MDA-MB-231 home to the brain in xenografted animals. To simultaneously capture gene expression changes in the tumor and stromal compartment, we used a dual species-specific microarray platform, the HuMuProtIn array, to discriminate between differentially expressed protease or protease inhibitor genes of human (tumor) or murine (stromal) origin. RNA was isolated from early and late brain, bone and lung metastases from xenograft models of breast metastasis. RNA was also isolated from non-tumor-burdened mouse brain, bone and lung as normal tissue controls. RNA from tissue homing cell lines was isolated in vitro to serve as a control for the human-derived RNA. Samples were collected from 24 total tumor-burdened mice, with 3 replicates for each condition and control. A total of 36 samples are included here.

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