The general interest of the Systems Oncology group is to understand how non-tumor cells contribute to tumor initiation, growth and metastasis. More than focusing on specific tumor types, the projects in the group aim in investigating the biological systems that support oncologic disease. For instance, by releasing soluble factors and/or extracellular vesicles, tumor cells can induce phenotypic modifications of stromal cells locally and at future sites of tumor dissemination (also known as pre-metastatic niches), which support tumor growth and metastasis. Extracellular vesicles isolated from liquid biopsies (such as plasma and other body fluids) are emerging as a powerful non-invasive and abundant source of information not only about tumor cells, but also potentially about how non-tumor cells respond/interact with malignant cells. By using animal models of tumor initiation, progression and metastasis, in combination with thorough analysis of extracellular vesicle composition isolated from patients with diverse clinical profiles, we intend to characterize novel cellular and molecular determinants of cancers.

Ongoing Projects:

Our overall goal is to investigate whether heathy tissues, locally and at distance, can contribute to tumor genesis, progression and metastasis, and if extracellular vesicles act as mediators of this process. For that, we are interested in:

(i) Novel tumor-associated cells: identify underappreciated non-malignant cellular counterparts (other than fibroblasts, endothelial cells and immune cells) susceptible to tumor-derived messages and with potential role as pro-tumor ancillary cells.

(ii) Stroma-tumor communication: identify messages (e.g. extracellular vesicles) derived from non tumor tissues, locally and at distance, that can influence tumor progression.

(iii) Phenotypic characterization of extracellular vesicles: by state-of-the-art flow cytometry in combination with detailed molecular characterization, identity extracellular vesicles subpopulations of different cell of origin and/or pathologic background relevant for tumor biology.

Bruno Costa-Silva, PhD
Principal Investigator
bruno.costa-silva@research.fchampalimaud.org

Biography

Bruna Ferreira, MD
PhD Student
bruna.ferreira@research.fchampalimaud.org

Joana Maia
GABBA PhD Student
joana.maia@research.fchampalimaud.org

Maria Carolina Strano Moraes, PhD
Research Assistant
carolina.stranomoraes@research.fchampalimaud.org

Lab Administration

Vesna Petojevic
Lab Administrator
vesna.petojevic@neuro.fchampalimaud.org

Tonielli Cristina Sousa de Lacerda, Bruno Costa-Silva, Fernanda Salgueiredo Giudice, Marcos Vinicios Salles Dias, Gabriela Pintar de Oliveira, Bianca Luise Teixeira, Tiago Goss dos Santos, Vilma Regina Martins. (2016) Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells Clin Exp Metastasis 33 , 441-451 (doi:10.1007/s10585-016-9788-8)

Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dum (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527 (7578), 329-335 (doi:10.1038/nature15756)

Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen TM, García-Santos G, Williams C, Ararso Y, Huang Y, Rodrigues G7, Shen TL, Labori KJ, Lothe IM, Kure EH, Hernandez J, Dousso (2015) Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat. Cell Biol. 17 (6), 816-826 (doi:10.1038/ncb3169)

Peinado H, Alekovi M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, García-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18 (6), 883-891 (doi:10.1038/nm.2753)