Laboratory of Stem Cells

Our main interest is the role of stem cells in physiological as well as pathological processes, such as cancer, by analyzing biomarkers which allow the detection of the most undifferentiated tumor phenotypes (tumor initiating cells) and the effects of the cellular/molecular microenvironment, mainly on driving metastasis during tumor evolution. We will take advantage of cell reprogramming technologies in order to study the metabolic reprogramming of tumors, independently of the physiopathological environment.     

Laboratory of Stem Cells

  • Norma Alejandra Chasseing / Dr. Juan Carlos Calvo

     

  • Teams

    Research Team: Mesenchymal/Stromal Stem Cells and Tumor Microenvironment

     

    Marcela F. Bolontrade, PhD. - Researcher from the Argentinean National Research Council (CONICET)


    Doctoral Fellows:

    MSc. in Biology, Amorós Mariana A. - CONICET Fellow

    MSc. in genetics, Gutiérrez Luciana M. - CONICET Fellow



     Research Team: Cancer Stem Cell and Metabolic Reprogrammation

     

    Luciano Vellón, PhD.

    PhD from the University of Buenos Aires School of Medicine (2003).

    Researcher from the Argentinean National Research Council (2014).

    María Paula Marks.

    Licentiate in genetics (equivalent to a Master degree) from the National University of Misiones (2013).

    Fellow from the National Cancer Institute from Argentina (2014).

     

Mesenchymal/Stromal Stem Cells and Tumor Microenvironment
Mesenchymal/Stromal Stem Cells and Tumor Microenvironment - Collaborations
Mesenchymal/Stromal Stem Cells and Tumor Microenvironment - International peer-reviewed journals
Mesenchymal/Stromal Stem Cells and Tumor Microenvironment - Book Chapters
Cancer Stem Cells and Metabolic Reprogramming

According to the cancer stem cell model (CSC), tumors comprise a subpopulation of cells able to self-renew and drive the processes of differentiation that contribute to tumor heterogeneity. CSCs are resistant to conventional therapies and are thought to be responsible for local relapse and metastatic recurrence during the evolution of several tumors, including breast cancer. Interestingly, the “CSC-state” seems to be a dynamic condition, capable of being acquired or lost by tumor cells. These changes include both epigenetic and metabolic reprogramming, the latter accomplished by the reactivation of key pathways, such as the mevalonic acid pathway, required for the synthesis of cholesterol and isoprenoids. To this regard, our area of research has three main stages:

1-Generation and characterization, by reprogramming technology, of putative models or “avatars” of CSCs, using cell lines derived from the different molecular subtypes of breast cancer.

2-Study the role of different components of the mevalonic acid (MVA) pathway during the acquirement of the CSC-state in cellular models of breast cancer.

3-Study the effects of inhibitors of key components of the MVA pathway during the establishment of the CSC phenotype.

 

Cancer Stem Cells and Metabolic Reprogramming - International peer-reviewed publications

1-MENENDEZ JA, SCHOEDER B, PEIRCE SK, VELLON L, PAPADIMITROPOULOU A, ESPINOZA I, LUPU R. Blockade of a key region in the extracellular domain inhibits HER2 dimerization and signaling. J Natl Cancer Inst (2015), 107(6): djv090. doi: 10.1093/jnci/djv090. Print 2015 Jun.

2-MENENDEZ JA, ALARCÓN T, COROMINAS-FAJA B, CUYÀS E, LÓPEZ-BONET E, MARTIN AG, VELLON L. Xenopatients 2.0: reprogramming the epigenetic landscapes of patient-derived cancer genomes. Cell Cycle (2014), 13 (3): 358-70.

3-VAZQUEZ-MARTIN A, CUFÍ S, LÓPEZ-BONET E, COROMINAS-FAJA B, CUYÀS E, VELLON L, IGLESIAS JM, LEIS O, MARTÍN AG, MENENDEZ JA. Reprogramming of non-genomic estrogen signaling by the stemness factor SOX2 enhances the tumor-initiating capacity of breast cancer cells. CellCycle (2013), 12(22): 3471-7.

4-COROMINAS-FAJA B, CUFÍ S, OLIVERAS-FERRAROS C, CUYÀS E, LÓPEZ-BONET E, LUPU R, ALARCÓN T, VELLON L, IGLESIAS JM, LEIS O, MARTÍN ÁG, VAZQUEZ-MARTIN A, MENENDEZ JA. Nuclear reprogramming of luminal-like breast cancer cells generates Sox2-overexpressing cancer stem-like cellular states harboring transcriptional activation of the mTOR pathway. Cell Cycle (2013), 12(18): 3109-24.

5-MANTEROLA L, HERNANDO-RODRÍGUEZ M, RUIZ A, APRAIZ A, ARRIZABALAGA O, VELLÓN L, ALBERDI E, CAVALIERE F, LACERDA HM, JIMENEZ S, PARADA LA, MATUTE C, ZUGAZA JL. 1-42 β-Amyloid peptide requires PDK1/nPKC/Rac 1 pathway to induce neuronal death. TranslPsychiatry (2013), 3:e219. doi: 10.1038/tp.2012.147. 

6-VAZQUEZ-MARTIN A, COROMINAS-FAJA B, CUFI S, VELLON L, OLIVERAS-FERRAROS C, MENENDEZ OJ, JOVEN J, LUPU R, MENENDEZ JA. The mitochondrial H (+) -ATP synthase and the lipogenic switch: New core components of metabolic reprogramming in induced pluripotent stem (iPS) cells. Cell Cycle (2013), 12(2): 207-18.

7-VAZQUEZ-MARTIN A, CUFI S, COROMINAS-FAJA B, OLIVERAS-FERRAROS C, VELLON L, MENENDEZ JA. Mitochondrial fusion by pharmacological manipulation impedes somatic cell reprogramming to pluripotency: new insight into the role of mitophagy in cell stemness. Aging (Albany NY) (2012), 4(6): 393-401.

8-CUFÍ S, VAZQUEZ-MARTIN A, OLIVERAS-FERRAROS C, QUITANTES R, SEGURA-CARRETERO A, MICOL V, JOVEN J, BOSCH-BARRERA J, DEL BARCO S, MARTIN-CASTILLO B, VELLON L, MENENDEZ JA. Metformin lowers the threshold for stress-induced senescence: A role for the microRNA-200 family and miR-205. Cell Cycle (2012), 11(6): 1235-46.

9-VAZQUEZ-MARTIN A, VELLÓN L, QUIRÓS PM, CUFÍ S, RUIZ DE GALARRETA E, OLIVERAS-FERRAROS C, MARTIN AG, MARTIN-CASTILLO B, LÓPEZ-OTÍN C, MENENDEZ JA. Activation of AMP-activated protein kinase (AMPK) provides a metabolic barrier to reprogramming somatic cells into stem cells. Cell Cycle (2012), 11(5): 974-89.

10-VAZQUEZ-MARTIN A, FERNÁNDEZ-ARROYO S, CUFÍ S, OLIVERAS-FERRAROS C, LOZANO-SÁNCHEZ J, VELLÓN L, MICOL V, JOVEN J, SEGURA-CARRETERO A, MENENDEZ JA. Phenolic Secoiridoids in Extra Virgin Olive Oil Impede Fibrogenic and Oncogenic Epithelial-to-Mesenchymal Transition: Extra Virgin Olive Oil As a Source of Novel Antiaging Phytochemicals. Rejuvenation Research (2012), 15(1): 3-21.

11-MENENDEZ JA, CUFÍ S, OLIVERAS-FERRAROS C, MARTIN-CASTILLO B, JOVEN J, VELLON L, VAZQUEZ-MARTIN A. Metformin and the ATM DNA damage response (DDR): accelerating the onset of stress-induced senescence to boost protection against cancer. Aging (Albany NY) (2011), 3(11): 1063-77.

12-MENENDEZ JA, CUFÍ S, OLIVERAS-FERRAROS C, MARTIN-CASTILLO B, JOVEN J, VELLON L, VAZQUEZ-MARTIN A. Metformin and the ATM DNA damage response (DDR): accelerating the onset of stress-induced senescence to boost protection against cancer. Aging (Albany NY)(2011), 3(11): 1063-77.

13-CUFÍ S, VAZQUEZ-MARTIN A, OLIVERAS-FERRAROS C, MARTIN-CASTILLO B, VELLON L, MENENDEZ JA. Autophagy positively regulates the CD44 (+) CD24 (-/low) breast cancer stem-like phenotype. Cell Cycle (2011), 10(22): 3871-85.

14-JAVIER A. MENENDEZ, LUCIANO VELLON, CRISTINA OLIVERAS-FERRAROS, SÍLVIA CUFÍ AND ALEJANDRO VAZQUEZ-MARTIN. mTOR-regulated senescence and autophagy during reprogramming of somatic cells to pluripotency: A roadmap from energy metabolism to stem cell renewal and aging. Cell Cycle (2011), 10 (21), 2011.

15-VELLON L, GARCIA-MARTIN A, Stem Cell Biobanks for Research. Dilemata (2011), 7: 1-16.

16- MENENDEZ JA, CUFÍ S, OLIVERAS-FERRAROS C, VELLON L, JOVEN J, VAZQUEZ-MARTIN A. Gerosuppressant metformin: less is more. Aging (Albany NY) (2011), 3(4): 348-62.

17-VELLON L, ROYO F, MATTHIESEN R, TORRES-FUENZALIDA J, LORENTI A, PARADA LA. Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells. BMC Cell Biol (2010), 11 (81). doi: 10.1186/1471-2121-11-81.

18-ROYO F, PAZ N, ESPINOSA L, MCQUEEN PG, VELLÓN L, PARADA LA. Spatial link between nucleoli and expression of the Zac1 gene. Chromosoma (2009), 118(6): 711-22.

19-COLOMER R, LUPU R, PAPADIMITROPOULOU A, VELLÓN L, VÁZQUEZ-MARTÍN A, BRUNET J, FERNÁNDEZ-GUTIÉRREZ A, SEGURA-CARRETERO A, MENÉNDEZ JA. GiacomoCastelvetro's salads.Anti-HER2 oncogene nutraceuticals since the 17th century? ClinTranslOncol (2008), 10(1): 30-4.

20-VELLON L, MENENDEZ JA, LIU H, LUPU R. Up-regulation of alphavbeta3 integrin expression is a novel molecular response to chemotherapy-induced cell damage in a heregulin-dependent manner. Differentiation (2007), 75(9): 819-30.

21-MENENDEZ JA, VELLON L, LUPU R. DNA Topoisomerase IIα (TOP2A) inhibitors up-regulate Fatty Acid Synthase (FAS) gene expression in SK-Br3 breast cancer cells: In vitro evidence for a “functional amplicon” involving FAS, Her-2/neu and TOP2A genes. International Journal of Molecular Medicine (2006), 18(6): 1081-7.

22-VELLON L, MENENDEZ JA, LUPU R.  A bidirectional "alpha(v)beta(3) integrin-ERK1/ERK2 MAPK" connection regulates the proliferation of breast cancer cells. Mol Carcinog. 2006, 45(10):795-804.

23-MENENDEZ JA, VELLON L, LUPU R. The anti-obesity drug Orlistat induces cytotoxic effects, suppresses Her-2/neu (erbB-2) oncogene overexpression, and synergistically interacts with trastuzumab (Herceptin) in chemoresistant ovarian cancer cells. International Journal of Gynecological Cancer (2006), 16(1): 219-21.

24-MENENDEZ JA, PAPADIMITROPOULOU A, VELLON L, LUPU R. A genomic explanation connecting "Mediterranean diet", olive oil and cancer: oleic acid, the main monounsaturated fatty acid of olive oil, induces formation of inhibitory "PEA3 transcription factor-PEA3 DNA binding site" complexes at the Her-2/neu (erbB-2) oncogene promoter in breast, ovarian and stomach cancer cells. Eur J Cancer 2006), 42(15): 2425-32.

25-MENENDEZ JA, VELLON L, COLOMER R, LUPU R. Effect of Gamma-Linolenic Acid on the transcriptional activity of the Her-2/neu (erbB-2) oncogene. Journal of the National Cancer Institute (2005), 97(21): 1611-5.

26-MENENDEZ JA, VELLON L, LUPU R. Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann Oncol (2005), 16(8): 1253-67.

27-VELLON L, MENENDEZ JA, LUPU R. αvβ3 Integrin Regulates Heregulin (HRG)-Induced Cell Proliferation and Survival in Breast Cancer. Oncogene (2005), 24(23): 3759-73.

28-MENENDEZ JA, VELLON L, LUPU R. Targeting Fatty Acid Synthase (FAS)-driven lipid rafts: A novel strategy to overcome trastuzumab resistance in breast cancer cells. Medical Hypotheses (2005), 64(5): 997-1001.

29-MENENDEZ JA, VELLON L, LUPU R. Orlistat: From anti-obesity drug to anti-cancer agent in Her-2/neu(erbB-2)-overexpressing gastrointestinal tumors? Experimental Biology and Medicine (Maywood)  (2005), 230(3): 151-4.

30-VELLON L, GONZALEZ CID M, de CAMPOS NEBEL M, LARRIPA I. Additive Apoptotic Effect Of STI-571 With The Cytoprotective Agent Amifostine In K-562 Cell Line Cancer Chem and Pharmacology (2005), 55(6): 602-8.

31-MENENDEZ JA, VELLON L, OZA BP, LUPU R. Does endogenous fatty acid metabolism allow cancer cells to sense hypoxia and mediate hypoxic vasodilatation? Characterization of a novel molecular connection between Fatty Acid Synthase (FAS) and Hypoxia-inducible factor-1α (HIF-1α)-related expression of Vascular Endothelial Growth Factor (VEGF) in cancer cells overexpressing HER-2/neuoncogene. Journal of Cellular Biochemistry (2005), 94(5): 857-63.

32-MENENDEZ JA, VELLON L, COLOMER R, LUPU R. Pharmacological and small interference RNA-mediated inhibition of breast cancer-associated fatty acid synthase (oncogenic antigen-519) synergistically enhances Taxol (paclitaxel)-induced cytotoxicity. International Journal of Cancer (2005), 115(1): 19-35.

33-MENENDEZ JA, VELLON L, COLOMER R, LUPU R. Oleic Acid, the main monoinsaturated fatty acido of Olive Oil, supresses Her-2/neu (erb-B2) expression and Synergistically enhances trastuzumab (HerceptinTM ) efficacy in Breast Cancer cells with Her-2/neu oncogene amplification. Ann Oncol (2005), 16(3): 359-71.

34-MENENDEZ JA, VELLON L, MEHMI I, TENG PK, GRIGGS D, LUPU R.A Novel CYR-61-Triggered “CYR-61- αvβ3 integrin loop” Regulates breast cancer cell survival and chemosensitivity Trough Activation of ERK1/ERK2 MAPK Signaling Pathway. Oncogene (2005), 24(5): 761-79.

35-MENENDEZ JA, VELLON L, MEHMI I, OZA BP, ROPERO S, COLOMER R, LUPU R. Pharmacological and Small Interference RNA-mediated Inhibition of Fatty Acid Synthase (FAS) Suppresses Overexpression of the HER-2/neu (erbB-2) Oncogene in Breast and Ovarian Cancer Cells. Proceedings of the NatlAcad of Sci (2004), 101 (29): 10715-20.

Cancer Stem Cells and Metabolic Reprogramming - Book chapters

Chapter: Cancer Stem Cells as a result of a reprogramming-like mechanism: implications in tumor development and treatment. IGLESIAS JM, GARCÍA-RAMÍREZ I, MARTÍN-LORENZO A, VELLON L, RUIZ-ROCA L, MARTIN AG Y SANCHEZ-GARCIA I. Book: Cancer Stem Cells. RAJASEKHAR VK. Wiley-Blackwell (2014).

Cancer Stem Cell and Metabolic Reprogramming - Grants

-“Alberto J. Roemmers Foundation” (2014-2016). Subject: Induced-pluripotent stem cells as tool for modeling breast cancer initiation and progression. Amount: $ 38.000. PI: Dr. Luciano Vellón. State: Ongoing.

 

-“Financial Aid to Cancer Research Projects of National Origin of the National Cancer Institute” (2014-2016). Subject: Induced-pluripotent stem cells as tool for modeling breast cancer initiation and progression. Amount: $ 250.000. PI: Dr. Luciano Vellón. State: Ongoing.

 

-“Saiotek  SPE11IB003 Program of the Department of Industry, Innovation, Commerce and Tourism  of the Basque Government, Spain” (2011-2012). Subject: Functional and structural genome reorganization of pluripotent cells. Amount: € 28.783,68. PI: Dr. Luciano Vellón. State: Finished.

 

 

Cancer Stem Cells and Metabolic Reprogramming - Awards

-“Diario Médico de España” Award to the best ideas during 2005, for the publication: Oleic Acid, the main monoinsaturated fatty acid of Olive Oil, supresses Her-2/neu (erb-B2) expression and Synergistically enhances trastuzumab (HerceptinTM ) efficacy in Breast Cancer cells with Her-2/neu oncogene amplification. Ann Oncol (2005), 16(3): 359-71.

-“Lucio Cherny” Award from the Argentinean Society for Clinical Research (Sociedad Argentina de Investigación Clínica, SAIC), 1999, for the work Antisense Oligonucletides increase idarubicin-induced apoptosis in the K-562 cell line.

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