Dataset Information

Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters.

ABSTRACT: Data from Massive, MSV000078535. MDAMB23 experiment: D101003_MDAMB231_1_OGE, file: D101003_MDAMB231_1_OGE02_rafkt_ft8_cc_01.mzml. Published as part of Elife. 2014 Mar 11;3:e01308 . From the Abstract: {{i}} In this study, we use proteomics to investigate the ECM of human mammary carcinoma xenografts and show that primary tumors of differing metastatic potential differ in ECM composition. Both tumor cells and stromal cells contribute to the tumor matrix and tumors of differing metastatic ability differ in both tumor- and stroma-derived ECM components. {{/i}}

INSTRUMENT(S): Instrument

ORGANISM(S): Homo_sapiens_viruses,mus_musculus_viruses, Human_female,mouse_female

DISEASE(S): Not Available

SUBMITTER: Naba A, et al.

PROVIDER: GPM32320002348 | GPMDB |

REPOSITORIES: GPMDB

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Publications

Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters.

Naba Alexandra A Clauser Karl R KR Lamar John M JM Carr Steven A SA Hynes Richard O RO

eLife 20140311

The extracellular matrix (ECM) is a major component of tumors and a significant contributor to cancer progression. In this study, we use proteomics to investigate the ECM of human mammary carcinoma xenografts and show that primary tumors of differing metastatic potential differ in ECM composition. Both tumor cells and stromal cells contribute to the tumor matrix and tumors of differing metastatic ability differ in both tumor- and stroma-derived ECM components. We define ECM signatures of poorly ...[more]

PMID: 24618895

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Project description:The invasive and metastatic spread of ovarian cancer (OC) results from the cooperative interactions between cancer and stroma, which include acellular extracellular matrix (ECM) and cellular components, such as cancer-associated fibroblasts (CAFs). Soluble growth factors secreted by cancer and stromal cells contribute to stroma remodeling through the synthesis and modification of ECM proteins, providing a favorable environment for cancer cell dissemination. Within the OC, the peptide endothelin-1 (ET-1), through two G protein-coupled receptors, ET A R and ET B R, supports tumor growth and progression by acting on both cancer and stromal cells. Many of these effects rely on the functional and molecular link with the protein b-arrestin1 (b-arr1). However, the precise role of ET-1 in regulating the expression of ECM proteins by primary human ovarian fibroblasts (HOFs) remains unclear. In this study, we aimed to elucidate the regulatory role of ET-1 in the expression of type I collagen (Col1) and fibronectin 1 (FN1). We report a significant increase in the expression of both Col1 and FN1 in cells stimulated with ET-1, both at mRNA and protein levels, reaching the amounts of proteins found in ovarian CAFs. The observed effects are associated with the activation of both receptors since they are impaired by treatment with either ET A R or ET B R antagonists in HOFs and CAFs. Furthermore, they are particularly affected by the dual ET A R/ET B R antagonist bosentan, in vitro and in vivo models. At the molecular level, ET-1 activates the Col1 promoter and enhances the expression of this gene through the nuclear function of β-arr1. The change in transcriptome of HOFs silenced for β-arr1 was analyzed to confirm the molecular response triggered by β-arr1, which resulted in the upregulation of ECM remodeling and collagen deposition. In summary, these findings demonstrate that the ET-1 axis may contribute to the remodeling of the ECM and probably to the early stages of OC progression by modulating the expression of Col1 and FN1. The targeting of ET-1 signaling with ET A R/ET B R antagonists may impede HOFs’ ability to produce key ECM proteins in this tumor.

Dataset Information

Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters.

Publications

Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters.

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