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
Juan García-Agulló
María Teresa González
Alberto Hernández

Technicians

Enrique Bastón
Sara Sánchez-Redondo
Vanesa Santos

Our Group aims to understand the crosstalk between tumour cells and their microenvironment during metastatic progression. Microenvironmental cues are important at all steps of the metastatic process, for which the recruitment of a variety of stromal cells is crucial. Secreted factors play an essential role in this mechanism including soluble factors and extracellular vesicles. These mechanisms of cell-cell communication have become as a novel language of cancer that we aim to decode. We are interested in: 1) understanding how tumour cells crosstalk with stromal cells involved in lymph node and distal metastasis in melanoma, lymphoma, prostate cancer and malignant peripheral nerve sheath tumours; 2) the influence of obesity in melanoma and breast cancer metastasis; and 3) the use of secreted extracellular vesicles (EVs) as surrogate markers of tumour progression. Our studies are focused on deciphering novel biomarkers of metastatic progression and the molecular mechanisms involved, with the aim to define novel therapeutic targets to block metastatic spread.

Publications

Verweij FJ, Balaj L, Boulanger CM, Carter DRF, Compeer EB, D'Angelo G, El Andaloussi S, Goetz JG, Gross JC, Hyenne V, Krämer-Albers EM, Lai CP, Loyer X, Marki A, Momma S, Nolte-'t Hoen ENM, Pegtel DM, Peinado H, Raposo G, Rilla K, Tahara H, Théry C, van Royen ME, Vandenbroucke RE, Wehman AM, Witwer K, Wu Z, Wubbolts R, van Niel G. (2021). The power of imaging to understand extracellular vesicle biology in vivo. Nat Methods 18, 1013-1026. 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 (2021). Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma. Mol Oncol 15, 407-428. CNIO Publication.
Guix FX, Capitán AM, Casadomé-Perales Á, Palomares-Pérez I, López Del Castillo I, Miguel V, Goedeke L, Martín MG, Lamas S, Peinado H, Fernández-Hernando C, Dotti CG. (2021). Increased exosome secretion in neurons aging in vitro by NPC1-mediated endosomal cholesterol buildup. Life Sci Alliance 4, e202101055. CNIO Publication.
García-Silva S, Ximénez-Embún P, Muñoz J, Peinado H (2021). Postlymphadenectomy Analysis of Exosomes from Lymphatic Exudate/Exudative Seroma of Melanoma Patients. Methods Mol Biol 2265, 345-359. CNIO Publication.
García-Silva S, Benito-Martín A, Nogués L, Hernández-Barranco A, Mazariegos MS, Santos V, Hergueta-Redondo M, Ximénez-Embún P, Kataru RP, Lopez AA, Merino C, Sánchez-Redondo S, Graña-Castro O, Matei I, Nicolás-Avila JÁ, Torres-Ruiz R, Rodríguez-Perales S, Martínez L, Pérez-Martínez M, Mata G, Szumera-Cieckiewicz A, Kalinowska I, Saltari A, Martínez-Gómez JM, Hogan SA, Saragovi HU, Ortega S, Garcia-Martin C, Boskovic J, Levesque MP, Rutkowski P, Hidalgo A, Muñoz J, Megías D, Mehrara BJ, Lyden D, Peinado H (2021). Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. Nat Cancer 2, 1387-1405. CNIO Publication.
Santos-Coquillat A, González MI, Clemente-Moragón A, González-Arjona M, Albaladejo-García V, Peinado H, Muñoz J, Ximénez Embún P, Ibañez B, Oliver E, Desco M, Salinas B. (2021). Goat Milk Exosomes As Natural Nanoparticles for Detecting Inflammatory Processes By Optical Imaging. Small 2, e2105421. CNIO Publication.
Olmeda D, Cerezo-Wallis D, Castellano-Sanz E, García-Silva S, Peinado H, Soengas MS (2021). Physiological models for in vivo imaging and targeting the lymphatic system: Nanoparticles and extracellular vesicles. Adv Drug Deliver Rev 175, 113833. CNIO Publication.
González Muñoz T, Amaral AT, Puerto-Camacho P, Peinado H, de Álava E (2021). Endoglin in the Spotlight to Treat Cancer. Int J Mol Sci 22, 3186. CNIO Publication.
González MI, González-Arjona M, Santos-Coquillat A, Vaquero J, Vázquez-Ogando E, de Molina A, Peinado H, Desco M, Salinas B (2021). Covalently Labeled Fluorescent Exosomes for In Vitro and In Vivo Applications. Biomedicines 9, 81. CNIO Publication.
Suárez H, Andreu Z, Mazzeo C, Toribio V, Pérez-Rivera AE, López-Martín S, García-Silva S, Hurtado B, Morato E, Peláez L, Arribas EA, Tolentino-Cortez T, Barreda-Gómez G, Marina AI, Peinado H, Yáñez-Mó M (2021). CD9 inhibition reveals a functional connection of extracellular vesicle secretion with mitophagy in melanoma cells. J Extracell Vesicles 10, e12082. CNIO Publication.
Hernández-Barranco A, Nogués L, Peinado H (2021). Could Extracellular Vesicles Contribute to Generation or Awakening of “Sleepy” Metastatic Niches?. Front Cell Dev Biol 9, 625221. CNIO Publication.
Villasante A, Godier-Furnemont A, Hernandez-Barranco A, Coq JL, Boskovic J, Peinado H, Mora J, Samitier J, Vunjak-Novakovic G (2021). Horizontal transfer of the stemness-related markers EZH2 and GLI1 by neuroblastoma-derived extracellular vesicles in stromal cells. Transl Res 237, 82-97. CNIO Publication.
García-Silva S, Gallardo M, Peinado H (2021). DNA-Loaded Extracellular Vesicles in Liquid Biopsy: Tiny Players With Big Potential?. Front Cell Dev Biol 8, 622579. CNIO Publication.
Royo F, Azkargorta M, Lavin JL, Clos-Garcia M, Cortazar AR, Gonzalez-Lopez M, Barcena L, Del Portillo HA, Yáñez-Mó M, Marcilla A, Borras FE, Peinado H, Guerrero I, Váles-Gómez M, Cereijo U, Sardon T, Aransay AM, Elortza F, Falcon-Perez JM (2021). Extracellular Vesicles From Liver Progenitor Cells Downregulates Fibroblast Metabolic Activity and Increase the Expression of Immune-Response Related Molecules. Front Cell Dev Biol 8, 613583. CNIO Publication.
Amor López A, Mazariegos MS, Capuano A, Ximénez-Embún P, Hergueta-Redondo M, Recio JÁ, Muñoz E, Al-Shahrour F, Muñoz J, Megías D, Doliana R, Spessotto P, Peinado H (2021). Inactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis. Int J Mol Sci 22, 7406. CNIO Publication.
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. Open Access
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. Open Access
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.