Theranostics 2022; 12(5):2150-2161. doi:10.7150/thno.64252 This issue

Research Paper

Exchange of cellular components between platelets and tumor cells: impact on tumor cells behavior

Alba Rodriguez-Martinez1,2*, Iris Simon-Saez1,3*, Sonia Perales1,3, Carmen Garrido-Navas1, Alessandro Russo4, Diego de Miguel-Perez4, Ignacio Puche-Sanz1,5, Clara Alaminos6, Jorge Ceron1,3, Jose A. Lorente1,2, Maria Pilar Molina1, Coral Gonzalez1, Massimo Cristofanilli7, Alba Ortigosa-Palomo1, Pedro J. Real1,3,8, Christian Rolfo4✉, María J. Serrano1,9,10✉

1. GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
2. Laboratory of Genetic Identification, Department of Legal Medicine, University of Granada, Granada, Spain.
3. Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Granada, Spain.
4. Center for Thoracic Oncology. The Tisch Cancer Institute. Icahn School of Medicine at Mount Sinai, New York, NY, USA.
5. Urology Department, University Hospital Virgen de las Nieves, Granada, Spain.
6. Urology Division, University Hospital of Jaén, Jaén, Spain.
7. Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
8. Instituto Biosanitario Granada (iBS-Granada), Granada, Spain.
9. Integral Oncology Division, Virgen de las Nieves University Hospital, Granada, Spain.
10. Department of Pathological Anatomy, Faculty of Medicine, University of Granada, Granada, Spain.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Rodriguez-Martinez A, Simon-Saez I, Perales S, Garrido-Navas C, Russo A, de Miguel-Perez D, Puche-Sanz I, Alaminos C, Ceron J, Lorente JA, Molina MP, Gonzalez C, Cristofanilli M, Ortigosa-Palomo A, Real PJ, Rolfo C, Serrano MJ. Exchange of cellular components between platelets and tumor cells: impact on tumor cells behavior. Theranostics 2022; 12(5):2150-2161. doi:10.7150/thno.64252. Available from https://www.thno.org/v12p2150.htm

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Abstract

Graphic abstract

Background: Platelets are active players in tumorigenesis, although the exact interactive mechanisms and their direct impact on tumor cells remain largely unknown.

Methods: Bidirectional transference of lipids, proteins and RNA between platelets and tumor cells and its impact on tumor cell behavior and tumor process are analyzed in this work. Phenotypic, genetic and functional modifications induced by platelets were analyzed both in tumor cell lines and in circulating tumor cells (CTCs).

Results: Data from these assays showed that platelets transferred structural components to tumor cells with higher efficiency than tumor cells to platelets (p = 0.001). This biological interplay occurred by direct contact, internalization or via extracellular vesicles. As a result, tumor cells acquired platelet markers (CD61 and CD42), showed decreased EpCAM, expressed epithelial-to-mesenchymal transition markers, and increased proliferation rates. Moreover, we were able to detect CD61 in CTCs from early and advanced prostate cancer.

Conclusions: Our results demonstrated, for the first time, that platelets educate tumor cells by highly efficient transference of lipids, proteins and RNA through different mechanisms. These results suggest that tumor cells and CTCs might acquire highly dynamic and aggressive phenotypes due to platelets interaction including EMT, stem-like phenotype and high proliferative rates.

Keywords: Platelets, circulating tumor cells (CTCs), platelet-educated tumors (PETs), epithelial-to-mesenchymal transition (EMT), CD61