Potential contrasting effects of platelets on the migration and invasion of sarcomas versus carcinomas

Abstract

The ability of platelets to promote carcinoma and melanoma progression has been thoroughly studied and occurs in numerous ways. In contrast, the effect of platelets on sarcomas, tumors arising from mesenchymal cells, has received very little attention. This study was undertaken to simultaneously compare the effects of platelets on murine and human sarcomas and carcinomas. In contrast to their effect on carcinomas, platelets inhibited the invasion of some murine- and all human sarcomas tested in vitro. Further invasion studies with TGFβ treatment only partially recapitulated the results seen with whole platelets. In a spontaneous tumor growth and lung metastasis model, platelets promoted 4T1 mammary carcinoma metastasis but not MCA-1 fibrosarcoma metastasis. Gene expression analysis of the platelet-promoted MDA-MB-231 breast carcinoma, and the platelet-inhibited HT1080 fibrosarcoma cell lines revealed that exposure of MDA-MB-231 to platelets, resulted in upregulation of oncogenes and EMT-associated genes whereas in HT1080 a tumor-suppressor gene was significantly upregulated. Thus, this study has revealed a potential diametrically opposing effect of platelets on mesenchymal and epithelial cancers, a finding that warrants further investigation.

Keywords:

• Carcinomas
• invasion
• migration
• platelets
• sarcomas

Acknowledgements

We thank Dr Grace Moshi and all of the volunteers of the Sarah Grace Sarcoma Foundation for their fundraising efforts to support this work and the PhD Scholarship of J Yoon, the staff of The John Curtin School of Medical Research for their assistance with imaging, pathology and flow cytometry facilities and the staff of the Animal Facility of the Australian National University.

Authorship Details

Conceptualization, J Yoon, CR Parish and LA Coupland.; methodology, J Yoon, CR Parish and LA Coupland; formal analysis, J Yoon and LA Coupland.; resources, CR Parish; data curation, J Yoon.; writing—original draft preparation, LA Coupland.; writing—review and editing, CR Parish, AC Blackburn and LA Coupland.; supervision, LA Coupland and CR Parish; project administration, CR Parish and LA Coupland; funding acquisition, CR Parish and LA Coupland.

Conflicts Of Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Supplementary Material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This research was funded by the Sarah Grace Sarcoma Foundation and a Program Grant from the Australian National Health & Medical Research Council, grant number [APP1052616].