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. 2017 Dec;10(1-3):1-7.
doi: 10.1007/s12307-017-0192-y. Epub 2017 Apr 13.

The Impact of Microenvironment on the Synovial Sarcoma Transcriptome

Huifeng Jin  1 , Jared J Barrott  1 , Matthew G Cable  1 , Michael J Monument  1 , Daniel M Lerman  1 , Kyllie Smith-Fry  1 , Dakota Nollner  1 , Kevin B Jones  2   3
Affiliations

The Impact of Microenvironment on the Synovial Sarcoma Transcriptome

Huifeng Jin et al. Cancer Microenviron. 2017 Dec.

Abstract

Synovial sarcoma (SS) is initiated by a t(X;18) chromosomal translocation and resultant SS18-SSX fusion oncogene. Only a few SS cell lines exist. None has been compared to its source tumor. In order to compare matched tumor and cell line pairs, we performed RNAseq on 3 tumor/cell line pairs from a genetically engineered mouse model of SS, as well as 2 pairs from human SS tumors. Transcriptomes of mouse tumors and derivative cell lines deviated significantly. Differentially expressed genes highlighted inflammatory infiltrates and metabolism. The same was found for the human tumor and cell line pairs. More was shared between different tumors than between any tumor and its cell line. Direct xenografting generated transcriptomes that more closely resembled the primary tumor than did its derivative cell line. SS tumor transcriptomes are powerfully impacted by the environment wherein they reside, especially with regard to immune interaction and metabolism.

Keywords: GEMM; Microenvironment; RNA transcriptome; Synovial sarcoma.

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Conflict of interest statement

Funding

This study was funded by The Paul Nabil Bustany Memorial Fund for Synovial Sarcoma Research, and partly by the Damon Runyon Cancer Research Foundation, P30CA042014 from the National Cancer Institute, the Huntsman Cancer Foundation, and 1S10RR026802–01 from the National Center for Research Resources.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Synovial sarcomas are comprised of a high percentage of tumor cells. a Photomicrographs of H&E histology examples of monophasic (MSS, left) and biphasic (BSS, right) SS18-SSX-induced synovial sarcomas from Myf5Cre-induced mice. b Photomicrographs following immunohistochemistry against GFP in MSS (left) and BSS (right) synovial sarcomas. c Pie charts demonstrating the percentage of GFP+ cells stained by IHC and counted in MSS (left) and BSS (right) mouse tumors. d Example flow cytometry of mouse MSS (left) and BSS (right) for intrinsic GFP signaling in tumor cells and E-cadherin-APC. (Magnification bars =50 μm)
Fig. 2
Fig. 2
Mouse and human synovial sarcoma transcriptional comparisons. a Heatmap demonstrating distribution of 10,833 and 8834 differentially expressed genes between tumors and cell lines from mice (left) and humans (right). b Venn diagrams showing significant overlapping genes between mouse (above) and human (below) samples, comparing cell lines to primary tumors. c Venn diagram showing 2-fold change overlapping genes shared as different in the same direction between the two primary tumor to xenograft comparisons from human tumors. d Hierarchal clustering of primary tumor and cell line transcriptome profiles for mouse and human samples, (left and right, respectively). T = primary tumor; C = cell line; X = xenograft
Fig. 3
Fig. 3
Pathways highlighted in genes differentially expressed between cell lines and tumors in synovial sarcoma. Results of quantitative IPA analysis
See this image and copyright information in PMC

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