Microenvironment & Metastasis Group

Hector Peinado Group Leader
T +34 (+34) 917 328 000 (Ext 3520)
hpeinado@cnio.es

Staff Scientists

Susana García

Post-Doctoral Fellows

Marta Hergueta
Laura Nogués

Graduate Students

María Elena Castellano
María Teresa González
Alberto Hernández

Technicians

Sara Sánchez-Redondo
Vanesa Santos

Our laboratory aims to understand how the microenvironment impacts metastatic behaviour. Most of the efforts in the past focused on defining intrinsic factors involved in tumour progression and metastasis. However, our interpretation of tumour evolution and metastasis has shifted and currently it is widely accepted that extrinsic factors are actively involved in cancer progression. To tackle this question, our laboratory uses melanoma models to define the role of secreted exosomes in pre-metastatic niche formation and metastasis in the lymph node. In addition, we are exploring the influence of obesity on the metastatic behaviour of melanoma and breast cancer. Finally, we are using novel therapeutic approaches to prevent metastasis in melanoma, lymphoma and malignant peripheral nerve sheath tumour metastasis by targeting both intrinsic and extrinsic factors.

Publications

Hoshino A, Kim HS, Bojmar L, Gyan KE, Cioffi M, Hernandez J, Zambirinis CP, Rodrigues G, Molina H, Heissel S, Mark MT, Steiner L, Benito-Martin A, Lucotti S, Di Giannatale A, Offer K, Nakajima M, Williams C, Nogués L, Pelissier Vatter FA, Hashimoto A, Davies AE, Freitas D, Kenific CM, Ararso Y, Buehring W, Lauritzen P, Ogitani Y, Sugiura K, Takahashi N, Aleckovic M, Bailey KA, Jolissant JS, Wang H, Harris A, Schaeffer LM, García-Santos G, Posner Z, Balachandran VP, Khakoo Y, Raju GP, Scherz A, Sagi I, Scherz-Shouval R, Yarden Y, Oren M, Malladi M, Petriccione M, De Braganca KC, Donzelli M, Fischer C, Vitolano S, Wright GP, Ganshaw L, Marrano M, Ahmed A, DeStefano J, Danzer E, Roehrl MHA, Lacayo NJ, Vincent TC, Weiser MR, Brady MS, Meyers PA, Wexler LH, Ambati SR, Chou AJ, Slotkin EK, Modak S, Roberts SS, Basu EM, Diolaiti D, Krantz BA, Cardoso F, Simpson AL, Berger M, Rudin CM, Simeone DM, Jain M, Ghajar CM, Batra SK, Stanger BZ, Bui J, Brown KA, Rajasekhar VK, Healey JH, de Sousa M, Kramer K, Sheth S, Baisch J, Pascual V, Heaton TE, La Quaglia MP, Pisapia DJ, Schwartz R, Zhang H, Liu Y, Shukla A, Blavier L, DeClerck YA, LaBarge M, Bissell MJ, Caffrey TC, Grandgenett PM, Hollingsworth MA, Bromberg J, Costa-Silva B, Peinado H, Kang Y, Garcia BA, O'Reilly EM, Kelsen D, Trippett TM, Jones DR, Matei IR, Jarnagin WR, Lyden D (2020). Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers. Cell 182, 1044-1061. CNIO Publication.
Fuentes P, Sesé M, Guijarro PJ, Emperador M, Sánchez-Redondo S, Peinado H, Hümmer S, Ramón Y Cajal S (2020). ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells. Nat Commun 11, 4261. CNIO Publication. Open Access
Toda H, Diaz-Varela M, Segui-Barber J, Roobsoong W, Baro B, Garcia-Silva S, Galiano A, Gualdrón-López M, Almeida ACG, Brito MAM, de Melo GC, Aparici-Herraiz I, Castro-Cavadía C, Monteiro WM, Borràs E, Sabidó E, Almeida IC, Chojnacki J, Martinez-Picado J, Calvo M, Armengol P, Carmona-Fonseca J, Yasnot MF, Lauzurica R, Marcilla A, Peinado H, Galinski MR, Lacerda MVG, Sattabongkot J, Fernandez-Becerra C, Del Portillo HA (2020). Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence. Nat Commun 11, 2761. CNIO Publication. Open Access
Galardi A, Colletti M, Lavarello C, Di Paolo V, Mascio P, Russo I, Cozza R, Romanzo A, Valente P, De Vito R, Pascucci L, Peinado H, Carcaboso AM, Petretto A, Locatelli F, Di Giannatale A. (2020). Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding. Cancers 12, E1555. CNIO Publication. Open Access
Ramón Y Cajal S, Sancho P, Soucek L, Peinado H, Abad M, Valiente M, Efeyan A, Pardo J, Quesada V, Jimeno J, Duque PM, Antón A, Varela I, Schuhmacher AJ (2020). A spotlight on cancer researchers in Spain: new paradigms and disruptive ideas. Clin Transl Oncol 22, 798-801. CNIO Publication.
Ma W, Gil HJ, Escobedo N, Benito-Martín A, Ximénez-Embún P, Muñoz J, Peinado H, Rockson SG, Oliver G (2020). Platelet factor 4 is a biomarker for lymphatic-promoted disorders.. JCI Insight 5, e135109. CNIO Publication.
Martinez-Lage M, Torres-Ruiz R, Puig-Serra P, Moreno-Gaona P, Martin MC, Moya FJ, Quintana-Bustamante O, Garcia-Silva S, Carcaboso AM, Petazzi P, Bueno C, Mora J, Peinado H, Segovia JC, Menendez P, Rodriguez-Perales S (2020). In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells. Nat Commun 11, 5060. CNIO Publication.
Colletti M, Tomao L, Galardi A, Paolini A, Di Paolo V, De Stefanis C, Mascio P, Nazio F, Petrini S, Castellano A, Russo I, Caruso R, Piga S, De Vito R, Pascucci L, Peinado H, Masotti A, Locatelli F, Di Giannatale A (2020). Neuroblastoma-secreted exosomes carrying miR-375 promote osteogenic differentiation of bone-marrow mesenchymal stromal cells. J Extracell Vesicles 9, 1774144. CNIO Publication.
Hergueta-Redondo M, Peinado H. (2020). The influence of secreted factors and extracellular vesicles in ovarian cancer metastasis. Ejc Suppl 15, 38-48. CNIO Publication.
Palacios-Ferrer JL, García-Ortega MB, Gallardo-Gómez M, García MÁ, Díaz C, Boulaiz H, Valdivia J, Jurado JM, Almazan-Fernandez FM, Arias-Santiago S, Amezcua V, Peinado H, Vicente F, Pérez Del Palacio J, Marchal JA. (2020). Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma. Mol Oncol 15, 407-428. CNIO Publication.
García-Silva S, Benito-Martín A, Sánchez-Redondo S, Hernández-Barranco A, Ximénez-Embún P, Nogués L, Mazariegos MS, Brinkmann K, Amor López A, Meyer L, Rodríguez C, García-Martín C, Boskovic J, Letón R, Montero C, Robledo M, Santambrogio L, Sue Brady M, Szumera-Cieckiewicz A, Kalinowska I, Skog J, Noerholm M, Muñoz J, Ortiz-Romero PL, Ruano Y, Rodríguez-Peralto JL, Rutkowski P, Peinado H (2019). Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAF V600E mutation. J Exp Med 216, 1061-1070. CNIO Publication.
Borghesan M, Fafián-Labora J, Eleftheriadou O, Carpintero-Fernández P, Paez-Ribes M, Vizcay-Barrena G, Swisa A, Kolodkin-Gal D, Ximénez-Embún P, Lowe R, Martín-Martín B, Peinado H, Muñoz J, Fleck RA, Dor Y, Ben-Porath I, Vossenkamper A, Muñoz-Espin D, O'Loghlen A (2019). Small Extracellular Vesicles Are Key Regulators of Non-cell Autonomous Intercellular Communication in Senescence via the Interferon Protein IFITM3.. Cell Reports 27, 3956-3971. CNIO Publication. Open Access
Capuano A, Pivetta E, Sartori G, Bosisio G, Favero A, Cover E, Andreuzzi E, Colombatti A, Cannizzaro R, Scanziani E, Minoli L, Bucciotti F, Amor Lopez AI, Gaspardo K, Doliana R, Mongiat M, Spessotto P (2019). Abrogation of EMILIN1-ß1 integrin interaction promotes experimental colitis and colon carcinogenesis. Matrix Biol 83, 97-115. CNIO Publication.
Colletti M, Paolini A, Galardi A, Di Paolo V, Pascucci L, Russo I, De Angelis B, Peinado H, De Vito R, Milano GM, Locatelli F, Masotti A, Di Giannatale A (2019). Expression profiles of exosomal miRNAs isolated from plasma of patients with desmoplastic small round cell tumor. Epigenomics 11, 489-500. CNIO Publication.
Gabandé-Rodríguez E, Pérez-Cañamás A, Soto-Huelin B, Mitroi DN, Sánchez-Redondo S, Martínez-Sáez E, Venero C, Peinado H, Ledesma MD (2019). Lipid-induced lysosomal damage after demyelination corrupts microglia protective function in lysosomal storage disorders. EMBO J 38, e99553. CNIO Publication.
Hyenne V, Ghoroghi S, Collot M, Bons J, Follain G, Harlepp S, Mary B, Bauer J, Mercier L, Busnelli I, Lefebvre O, Fekonja N, Garcia-Leon MJ, Machado P, Delalande F, López AA, Silva SG, Verweij FJ, van Niel G, Djouad F, Peinado H, Carapito C, Klymchenko AS, Goetz JG (2019). Studying the Fate of Tumor Extracellular Vesicles at High Spatiotemporal Resolution Using the Zebrafish Embryo. Dev Cell 48, 554-572. CNIO Publication.
Rodrigues G, Hoshino A, Kenific CM, Matei IR, Steiner L, Freitas D, Kim HS, Oxley PR, Scandariato I, Casanova-Salas I, Dai J, Badwe CR, Gril B, Tešic Mark M, Dill BD, Molina H, Zhang H, Benito-Martin A, Bojmar L, Ararso Y, Offer K, LaPlant Q, Buehring W, Wang H, Jiang X, Lu TM, Liu Y, Sabari JK, Shin SJ, Narula N, Ginter PS, Rajasekhar VK, Healey JH, Meylan E, Costa-Silva B, Wang SE, Rafii S, Altorki NK, Rudin CM, Jones DR, Steeg PS, Peinado H, Ghajar CM, Bromberg J, de Sousa M, Pisapia D, Lyden D (2019). Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis.. Nat Cell Biol 21, 1403-1412. CNIO Publication.
Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z, Chen H, Mark MT, Molina H, Martin AB, Bojmar L, Fang J, Rampersaud S, Hoshino A, Matei I, Kenific CM, Nakajima M, Mutvei AP, Sansone P, Buehring W, Wang H, Jimenez JP, Cohen-Gould L, Paknejad N, Brendel M, Manova-Todorova K, Magalhães A, Ferreira JA, Osório H, Silva AM, Massey A, Cubillos-Ruiz JR, Galletti G, Giannakakou P, Cuervo AM, Blenis J, Schwartz R, Brady MS, Peinado H, Bromberg J, Matsui H, Reis CA, Lyden D (2018). Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol 20, 332-343. CNIO Publication.
Casanova-Acebes M, Nicolás-Ávila JA, Li JL, García-Silva S, Balachander A, Rubio-Ponce A, Weiss LA, Adrover JM, Burrows K, A-González N, Ballesteros I, Devi S, Quintana JA, Crainiciuc G, Leiva M, Gunzer M, Weber C, Nagasawa T, Soehnlein O, Merad M, Mortha A, Ng LG, Peinado H, Hidalgo A (2018). Neutrophils instruct homeostatic and pathological states in naive tissues. J Exp Med 215, 2778-2795. CNIO Publication.
Nogués L, Benito-Martin A, Hergueta-Redondo M, Peinado H (2018). The influence of tumour-derived extracellular vesicles on local and distal metastatic dissemination. Mol Aspects Med 60, 15-26. CNIO Publication.
Di Paolo V, Russo I, Boldrini R, Ravà L, Pezzullo M, Benedetti MC, Galardi A, Colletti M, Rota R, Orlando D, Crocoli A, Peinado H, Milano GM, Di Giannatale A (2018). Evaluation of Endoglin (CD105) expression in pediatric rhabdomyosarcoma. Bmc Cancer 18, 31. CNIO Publication. Open Access
García-Rodríguez A, de la Casa M, Peinado H, Gosálvez J, Roy R (2018). Human prostasomes from normozoospermic and non-normozoospermic men show a differential protein expression pattern. Andrology 6, 585-596. CNIO Publication.
Robado de Lope L, Alcíbar OL, Amor López A, Hergueta-Redondo M, Peinado H (2018). Tumour-adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles. Philos Trans R Soc Lond B Biol Sci. 373, pii: 20160485. CNIO Publication.
Santamaría PG, Floristán A, Fontanals-Cirera B, Vázquez-Naharro A, Santos V, Morales S, Yuste L, Peinado H, García-Gómez A, Portillo F, Hernando E, Cano A (2018). Lysyl oxidase-like 3 is required for melanoma cell survival by maintaining genomic stability. Cell Death Differ 25, 935-950. CNIO Publication.
Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A, Rodrigues G, Psaila B, Kaplan RN, Bromberg JF, Kang Y, Bissell MJ, Cox TR, Giaccia AJ, Erler JT, Hiratsuka S, Ghajar CM, Lyden D (2017). Pre-metastatic niches: organ-specific homes for metastases.. Nat Rev Cancer 17, 302-317. CNIO Publication.
Huang Y, Rajappa P, Hu W, Hoffman C, Cisse B, Kim JH, Gorge E, Yanowitch R, Cope W, Vartanian E, Xu R, Zhang T, Pisapia D, Xiang J, Huse J, Matei I, Peinado H, Bromberg J, Holland E, Ding BS, Rafii S, Lyden D, Greenfield J (2017). A proangiogenic signaling axis in myeloid cells promotes malignant progression of glioma. J Clin Invest 127, 1826-1838. CNIO Publication.
A Gonzalez N, Quintana JA, García-Silva S, Mazariegos M, González de la Aleja A, Nicolás-Ávila JA, Walter W, Adrover JM, Crainiciuc G, Kuchroo VK, Rothlin CV, Peinado H, Castrillo A, Ricote M, Hidalgo A (2017). Phagocytosis imprints heterogeneity in tissue-resident macrophages. J Exp Med 214, 1281-1296. CNIO Publication.
Colletti M, Petretto A, Galardi A, Di Paolo V, Tomao L, Lavarello C, Inglese E, Bruschi M, Lopez AA, Pascucci L, Geoerger B, Peinado H, Locatelli F, Di Giannatale A (2017). Proteomic Analysis of Neuroblastoma-Derived Exosomes: New Insights into a Metastatic Signature.. Proteomics 17, 23-24. CNIO Publication.
Pathan M1, Keerthikumar S1, Chisanga D2, Alessandro R3, Ang CS4, Askenase P5, Batagov AO6, Benito-Martin A7, Camussi G8, Clayton A9, Collino F8,10, Di Vizio D11, Falcon-Perez JM12, Fonseca P13, Fonseka P1, Fontana S3, Gho YS14, Hendrix A15, Hoen EN16, Iraci N17,18, Kastaniegaard K19, Kislinger T20, Kowal J21, Kurochkin IV6, Leonardi T18,22, Liang Y23, Llorente A24,25, Lunavat TR26, Maji S27, Monteleone F3, Øverbye A24,25, Panaretakis T13, Patel T27, Peinado H7,28, Pluchino S18, Principe S20, Ronquist G29, Royo F12, Sahoo S23, Spinelli C11, Stensballe A19, Théry C21, van Herwijnen MJC16, Wauben M16, Welton JL30, Zhao K1, Mathivanan S (2017). A novel community driven software for functional enrichment analysis of extracellular vesicles data. J Extracell Vesicles 6, 1321455. CNIO Publication.
Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D (2016). Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis.. Cancer Cell 30, 836-848. CNIO Publication.
García-Silva S, Peinado H (2016). Melanosomes foster a tumour niche by activating CAFs.. Nat Cell Biol 18, 911-913. CNIO Publication.
Zhou J,Ghoroghi S, Benito-Martin A, Wu H1, Unachukwu UJ, Einbond LS, Guariglia S, Peinado H, Redenti S (2016). Characterization of Induced Pluripotent Stem Cell Microvesicle Genesis, Morphology and Pluripotent Content. Sci Rep 6, 19743. CNIO Publication. Open Access
Torrano V, Royo F, Peinado H, Loizaga-Iriarte A, Unda M, Falcón-Perez JM, Carracedo A. (2016). Vesicle-MaNiA: extracellular vesicles in liquid biopsy and cancer.. Curr Opin Pharmacol 29, 47-53. CNIO Publication.
Veerappan A, Thompson M, Savage AR, Silverman ML, Chan WS, Sung B, Summers B, Montelione KC, Benedict P, Groh B, Vicencio AG, Peinado H, Worgall S, Silver RB (2016). Mast cells and exosomes in hyperoxia-induced neonatal lung disease.. Am J Physiol-Lung C 310, L1218-L1232. CNIO Publication.