In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 1_Supplement ( 2015-01-01), p. A43-A43
Abstract:
Cancer progression is critically dependent on specific molecular interactions between tumor cells and their microenvironment, but little is known about the global dynamics of this crosstalk within and across individuals. Here, we used an RNA sequencing approach with species-of-origin information in a xenograft mouse model to computationally resolve and compare tumor versus stromal transcriptional changes. Our study employed a triple-negative breast cancer (TNBC) model in which primary tumor invasiveness is controlled by the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP) allowing systemic observation of stromal response to invasive or noninvasive breast tumours at both proximal and distal sites. Initially, we observed that expression levels of gene homologs in human tumor and mouse stroma are highly synchronized. Surprisingly, the set of genes most prognostic for metastasis-free survival in multiple clinical data sets were those whose mRNA expression was inversely correlated between tumor and stroma. These results were confirmed in an independent set of microarray data from tumor and stroma micro-dissected from primary human breast cancer patient tissue. Additionally, we found broad-based and invasion-specific gene expression changes in stromal tissues far from the primary lesion, with these results being confirmed in an independent set of samples. Of note, genes differentially expressed in the tumor-associated stroma were better classifiers of tumor phenotype than genes differentially expressed in the tumor alone. As well, stromal genes differentially expressed both locally and distally, are significant predictors of patient prognosis. These findings demonstrate the potential for using patient tissue remote from the primary tumor as indicators of disease aggressiveness. Furthermore, these results suggest that stromal gene expression, acting to compensate for changes in the tumor, may have both prognostic and therapeutic implications. Citation Format: Casey A. Frankenberger, Russell O. Bainer, Daniel C. Rabe, Sadiq Saleh, Morag Park, Yoav Gilad, Marsha R. Rosner. Systemic tumor-stroma interactions are prognostic indicators of breast tumor invasiveness. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A43. doi:10.1158/1538-7445.CHTME14-A43
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.CHTME14-A43
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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