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Dott.ssa Moitza Principe

  • Dottorato: 26° ciclo
  • Matricola: 283276

Contatti

Supervisore

Francesco Novelli

Tesi di dottorato

TESI DI DOTTORATO

Alpha-Enolase

as immunological and molecular target for pancreatic cancer therapy

Tutor: Prof. FRANCESCO NOVELLI

Coordinator:  Prof.ssa MIRELLA GIOVARELLI

Attività di ricerca

 

The aim of this thesis is to elucidate the multifunctional role of alpha-Enolase (ENO1) in Pancreatic Cancer. Based on the literature, plasminogen receptors were expressed on the cell surface of most tumors, so the idea of delineating new personalized therapeutic strategies to counteract tumor growth and metastasis by targeting different plasminogen receptors ENO1, ANX2 and CK8, alone or in combination. To do this we used in the following experimental study a monoclonal antibody that specifically targets ENO1. Our findings strongly suggest that anti-ENO1 mAb blocks the surface ENO1/plasminogen interaction, and consequently inhibits the plasminogen-dependent invasion of PDAC cells and metastatic process in vivo. To deeply understand the ENO1 role in Pancreatic Cancer, the protein was silenced and the effects were evaluated. Proteomic analysis after silencing revealed a modulation of many proteins involved in cell metabolism, transport, cell proliferation, cell adhesion and migration. A second study demonstrated that the depletion of total ENO1 causes a remodeling of the cytoskeleton structure and reduces migration and invasion capability as well as tumor growth. Lastly, we though to exploit ENO1 as a Tumor Associated Antigen (TAA) to design novel therapeutic strategies. In a third study we demonstrated that a DNA-based vaccination against human ENO1 significantly prolongs the median of life expectancy of mice that spontaneously develop PDAC by stimulating anti-tumor immunity. All together our results confirm the idea that ENO1 is a promising molecular and immunological target.

Another potential target may be represented by PCAA14, an hypothetical protein that has been associated with the PDAC due to the presence of autoantibodies against it specifically in PDAC patients. My contribution in the study focused on its characterization allowed to demonstrate its role as tumor-suppressive protein in Pancreatic Cancer, although we need to go deeply in the story.

Vaccination with ENO1 DNA prolongs survival of genetically engineered mice with pancreatic cancer.

Cappello P, Rolla S, Chiarle R, Principe M, Cavallo F, Perconti G, Feo S, Giovarelli M, Novelli F.

Gastroenterology. 2013 May;144(5):1098-106. doi: 10.1053/j.gastro.2013.01.020. Epub 2013 Jan 16.

PMID: 23333712

 

Three are better than one: plasminogen receptors as cancer theranostic targets.

Ceruti P, Principe M, Capello M, Cappello P, Novelli F.

Exp Hematol Oncol. 2013 Apr 17;2(1):12. doi: 10.1186/2162-3619-2-12.

PMID: 23594883
 
 

 

1) XXXIII° National Congress of the Italian Association for the Study of the Pancreas (AISP), October 15-17, 2009, Rozzano, Milano (Italy).

BLOCKADE OF PLASMINOGEN- ALPHA- ENOLASE INTERACTION INHIBITS PANCREATIC CANCER CELL LINES INVASION

Ceruti P, Cappello P, Principe M, Novelli F

 

2) Targeting Cancer Invasion and Metastasis, February 21-24, 2010, Miami Beach, Florida, USA

THE BLOCKADE OF PLASMINOGEN-ALPHA-ENOLASE INTERACTION INHIBITS THE INVASION OF PANCREATIC CANCER CELLS

Patrizia Ceruti, Paola Cappello, Michelle Samuel Chattaragada, Moitza Principe, Jorg Hamm, Simona Rolla, Franco Novelli

 

3) Pancreatology 2010; 10:259-400 42nd European Pancreatic Club (EPC) Meeting, June 16-19, 2010, Stockholm, Sweden

THE BLOCKADE OF PLASMINOGEN-ALPHA-ENOLASE INTERACTION INHIBITS THE INVASION OF PANCREATIC CANCER CELLS

Patrizia Ceruti, Michelle Samuel Chattaragada, Paola Cappello, Moitza Principe, Jorg Hamm, Simona Rolla, Franco Novelli

 

4) HUPO 10th Annual World Congress, Geneva (Switzerland), 4-7 September 2011.

CHARACTERIZATION OF CIRCULATING AUTOANTIBODIES TO POST-TRANSLATIONALLY MODIFIED ALPHA-ENOLASE IN PANCREATIC DUCTAL ADENOCARCINOMA

S. Ferri-Borgogno, M. Capello, W. Zhou, C. Fredolini, M. Principe, P. Cappello, A. Scarpa, P. Nisticò, M. Milella, E. Petricoin, F. Novelli (2011).

 

5) AACR Special Conference “Pancreatic Cancer: Progress and Challenges”, June 18-21, 2012, Lake Tahoe, Nevada

EFFECT OF ALPHA-ENOLASE SILENCING IN ADENOCARCINOMA PANCREATIC CELL LINE

Principe M, Capello M, Chattaragada MS, Zhou W, Liotta LA, Petricoin EF, Novelli F

 

6) Keystone Simposia "Antibodies as Drugs", January 27 - February 1, 2013, Vancouver, British Columbia, Canada

Anti-alpha-Enolase antibody blocks Plasminogen-Alpha-Enolase interaction and inhibits the invasion of Pancreatic Cancer cells

M Principe, P Ceruti, L Conti, J Hamm, , S Rolla, P Cappello, F Novelli

 

7) Keystone Simposia "Cancer Immunology and Immunotherapy", January 27 - February 1, 2013, Vancouver, British Columbia, Canada   

DNA VACCINATION WITH ALPHA-ENOLASE SIGNIFICANTLY DELAYS TUMOR PROGRESSION BY ELICITING COMPLEMENT-DEPENDENT CYTOTOXICITY

Paola Cappello, Simona Rolla, Roberta Curto, Moitza Principe, Helen Carnevale, Mirella Giovarelli, Francesco Novelli

 

8) Keystone Simposia " Tumor metabolism", February 24 - March 1, 2013, Keystone, Colorado, USA

The moonlighting glycolytic enzyme α-enolase as a therapeutic target in pancreatic cancer

Capello M, Principe M, Chattaragada MS, Riganti C, Zhou W, Ferri-Borgogno S, Rolla S, Liotta LA, Petricoin EF, Cappello P, Novelli F

 

9) AACR Annual Meeting 2013, April 6-10, 2013, Washington DC, USA

Can the moonlighting glycolytic enzyme α-enolase be a therapeutic target in pancreatic cancer?

Capello M, Principe M, Chattaragada MS, Riganti C, Zhou W, Ferri-Borgogno S, Rolla S, Liotta LA, Petricoin EF, Cappello P, Novelli F

 

10) Pancreatic Cancer Meeting, June 20-21, 2013. Salerno, Italy

Can the moonlighting glycolytic enzyme α-enolase be a therapeutic target in pancreatic cancer?

Michela Capello, Moitza Principe, Chiara Riganti, Weidong Zhou, Michelle S Chattaragada, Sammy Ferri-Borgogno, Simona Rolla, Lance A Liotta, Emanuel F Petricoin, Paola Cappello, Francesco Novelli

 

11) ICI2013 International Congress of Immunology, August 22-27, 2013, Milano, Italy

ENO1-DNA vaccine significantly delays pancreatic tumor progression by eliciting complement-dependent cytotoxicity

Paola Cappello, Simona Rolla, Roberta Curto, Moitza Principe, Helen Carnevale, Mirella Giovarelli, Francesco Novelli

 

12) 21st Annual Cancer Research Institute International Cancer Immunotherapy Symposium "Cancer Immunotherapy 2013- Dynamics of Host-Tumor Interaction", September 30 - October 02, 2013, New York, NY, USA

Blockade of interaction between alpha-Enolase plasminogen inhibits the invasion of pancreatic cancer cells in vitro and in vivo

Patrizia Ceruti 1,2, Moitza Principe 1,2, Michelle S.Chattaragada 1,2, Simona Rolla 1,2, Laura Conti 2, Marco Bestagno 3, Paola Cappello 1,2, Oscar Burrone 3, Francesco Novelli 1,2

 

13) Second  Ascoli Piceno Conference on “Gene Vaccination in Cancer”, October 9-11, 2013, Ascoli Piceno, Italy (Selected for oral presentation, and First prize awarded for the best abstract presented by scientists aged under 35).

Anti-alpha-Enolase antibody blocks Plasminogen-Alpha-Enolase interaction and inhibits the invasion of Pancreatic Cancer cells

Moitza Principe1,2(under 35, moitza.principe@unito.it), Patrizia Ceruti1,2, Simona Rolla1,2, Laura Conti2, Marco Bestagno3, Paola Cappello1,2, Oscar Burrone3, Franco Novelli1,2

 

14) SIICA "Giornata nazionale dei dottorati di immunologia", 10-11 Ottobre 2014, Bari (POSTER)

Abstract: Targeting of surface ENO1 inhibits the invasiveness of pancreatic cancer cells

Moitza Principe1,2,†, Patrizia Ceruti1,2,†, Simone Borgoni1,2, Michela Capello1,2, Michelle S. Chattaragada1,2, Sammy Ferri-Borgogno1,2, Simona Rolla1,2, Laura Conti2,3, Marco Bestagno4, Lorena Zentilin4, Paola Migliorini5, Weidong Zhou6, Emanuel F Petricoin6, Paola Cappello1,2, Oscar Burrone4, Francesco Novelli1,2

 

 

DOCUMENTAZIONE RELATIVA ALLA PARTECIPAZIONE AD ATTIVITA’ FORMATIVE NELL’ANNO 2014

 - SIICA "Giornata nazionale dei dottorati di immunologia", 10-11 Ottobre 2014, Bari (POSTER)

Abstract: Targeting of surface ENO1 inhibits the invasiveness of pancreatic cancer cells

Moitza Principe1,2,†, Patrizia Ceruti1,2,†, Simone Borgoni1,2, Michela Capello1,2, Michelle S. Chattaragada1,2, Sammy Ferri-Borgogno1,2, Simona Rolla1,2, Laura Conti2,3, Marco Bestagno4, Lorena Zentilin4, Paola Migliorini5, Weidong Zhou6, Emanuel F Petricoin6, Paola Cappello1,2, Oscar Burrone4, Francesco Novelli1,2

 

DOCUMENTAZIONE RELATIVA ALLA PARTECIPAZIONE AD ATTIVITA’ FORMATIVE NELL’ANNO 2013

- Keystone Symposia “Antibodies as drugs”, January 27- February 1, 2013, Vancouver, British Columbia, Canada (POSTER)

Anti-alpha-Enolase antiboby blocks Plasminogen-alpha-Enolase interaction and inhibits the invasion of Pancreatic Cancer cells

Moitza Principe1,2, Patrizia Ceruti1,2, Laura Conti3, Jorg Hamm3, Simona Rolla1,2, Paola Cappello1,2, Franco Novelli1,2

1Center for Experimental Research and Medical Studies (CeRMS), Azienda Ospedaliera Città della Salute e della Scienza, 2Department of Molecular Biotechnology and Health Science, 3Molecular Biotechnology Center (MBC), University of Turin, Turin, Italy

 

- 3rd General Assembly Meeting EPC-TM-Net “Targeting the tumor microenvironment to improve Pancreatic Cancer Prognosis”, February 2013.Verona (Italy)

 

- Second  Ascoli Piceno Conference on “Gene Vaccination in Cancer”, October 9-11, 2013, Ascoli Piceno, Italy (POSTER; selected for oral presentation, and First prize awarded for the best abstract presented by scientists aged under 35)

Anti-alpha-Enolase antibody blocks Plasminogen-Alpha-Enolase interaction and inhibits the invasion of Pancreatic Cancer cells

Moitza Principe1,2(under 35, moitza.principe@unito.it), Patrizia Ceruti1,2, Simona Rolla1,2, Laura Conti2, Marco Bestagno3, Paola Cappello1,2, Oscar Burrone3, Franco Novelli1,2

1Center for Experimental Research and Medical Studies (CeRMS), Azienda Ospedaliera Città della Salute e della Scienza di Torino, Italy; 2Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy; 3 International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy

 

DOCUMENTAZIONE RELATIVA ALLA PARTECIPAZIONE AD ATTIVITA’ FORMATIVE NELL’ANNO 2012

- Congress: AACR Special Conference “Pancreatic Cancer: Progress and Challenges”, June 18-21, 2012, Lake Tahoe, Nevada (POSTER)

Abstract: EFFECT OF ALPHA-ENOLASE SILENCING IN ADENOCARCINOMA PANCREATIC CELL LINE

Principe M§, Capello M§, Chattaragada MS§, Zhou W‡, Liotta LA‡, Petricoin EF‡, Novelli F§

§Center for Experimental Research and Medical Studies (CeRMS) and University of Turin, San Giovanni Battista Hospital, Turin, Italy ‡Center for Applied Proteomics ad Molecular Medicine, George Mason University, Manassas, Virginia, United States

 

DOCUMENTAZIONE RELATIVA ALLA PARTECIPAZIONE AD ATTIVITA’ FORMATIVE NELL’ANNO 2011

 

DOCUMENTAZIONE RELATIVA ALLA PARTECIPAZIONE AD ATTIVITA’ FORMATIVE NELL’ANNO 2014

- Seminario di Dipartimento: "Stemness, reprogramming, regenerative medicine",  13 Febbraio 2014, Aula Darwin, MBC, Via Nizza 52, Torino

- Workshop: “Mechanisms of Cell Mechanosensing”, 4 Marzo 2014, Aula Cappa – IRCC, Candiolo (TO)

 - Seminario di Dipartimento: "Inflammation and immunotherapy",  20 Marzo 2014, Aula Darwin, MBC, Via Nizza 52, Torino

 - Seminario di Dipartimento: "From Chemistry to Biology", 10 Aprile 2014, Aula Copernico, MBC, Via Nizza 52, Torino

- Seminario di Dipartimento: "Brain Storming - Neuroscience", 15 maggio 2014, Aula Darwin, MBC, Via Nizza 52, Torino

- Seminario (ADE di Medicina e Chirurgia) Dott.sa Federica Marchesi "Microambiente Immunitario: nuovi marcatori prognostici e target terapeutici", 13 giugno 2014, Aula di Patologia, Via Santena 5, Torino 

- Seminario (ADE di Medicina e Chirurgia) Dott.sa Paola Nisticò "Ruolo del Sistema Immunitario nella Terapia dei Tumori", 13 giugno 2014, Aula di Patologia, Via Santena 5, Torino

  - Workshop SIC: "“Targeted Therapy of Cancer: where we are heading”, 27 giugno 2014, Aula Keplero, MBC, Via Nizza 52, Torino

- Seminario di Dipartimento: "Unmet clinical needs: Basic Scientists meet Clinicians to fill the gap", 29 ottobre 2014, Aula Aristotele, MBC, Via Nizza 52, Torino

 

PARTECIPAZIONE AD ATTIVITA’ FORMATIVE NELL’ANNO 2013

- Seminario: Raffaele De Palma " Human Th17: Origin, Differentiation and Disease”, 9 Gennaio 2013, Aula CeRMS, via Santena 5, Torino

Seminario: Michele De Luca "Regenerative Medicine by somatic stem cells: the paradigm of epithelial stem cells", 15 Gennaio 2013, MBC, Via Nizza 52, Torino

- Seminario: Filippo Giancotti "Mechanisms governing metastatic dormancy and reactivation”, 21 Gennaio 2013, MBC, Via Nizza 52, Torino

- Seminario: Laurence C. Eisenlohr "Where Do MHC Class II-bound Peptides Come From? Implications for Immunity to Viruses, Self and Cancer”, 6 Maggio 2013, MBC, Via Nizza 52, Torino

- "D-DAY", 11 Giugno 2013, Aula Magna del Rettorato, Via Verdi 8, Torino

- Workshop: " Label-free Biomolecular Interactions in Real-Time", 11-14 Novembre 2013, Department of Molecular Biotechnology and Health Science, Via Nizza 52, Turin (ITALY)

- Seminario di Dipartimento: "Cancer onset, progression and metastasis ",  19 Dicembre 2013, Aula Darwin, MBC, Via Nizza 52, Torino

 

DOCUMENTAZIONE RELATIVA ALLA PARTECIPAZIONE AD ATTIVITA’ FORMATIVE NELL’ANNO 2012

- Seminario: Pier Paolo Di Fiore "Endocytosis, Stem cells and Cancer", 11 gennaio 2012 presso l'MBC, Via Nizza 52, Torino

- Seminario: Ario De Marco "Biomedical application of the recombinant antibodies technology", 19 gennaio 2012 presso l'MBC, Via Nizza 52, Torino

- Seminario: Pier Giuseppe Pelicci "Regulation of Self-renewal in Cancer stem cells", 25 gennaio 2012 presso l'MBC, Via Nizza 52, Torino

- Seminario: Giuseppe Maruccio "Multipurpose biochips toward on-chip medicine", 31 gennaio 2012 presso l'Ospedale San Giovanni Battista

- Corso: Prof. Paolo Provero, Corso di biostatistica “Statistica per l’analisi di dati di interesse biologico”, 27-28 Febbraio 2012, presso l'MBC, Via Nizza 52, Torino

- Seminario: Ethan M Shevach “Foxp3+ T Regulatory Cells: What do they really do?”, 27 Marzo 2012 presso MBC, Via Nizza 52, Torino

- Seminario: Manuel Hidalgo “Pancreatic Cancer: from molecular understanding to personal treatment”, 13 Aprile 2012, IRCC, Candiolo

- Workshop: “Cancer Day: From Metabolism to Immunotherapy”, 7 Giugno 2012, MBC Via Nizza 52, Torino

- "D-Day”, 14 Settembre, Aula Magna del Rettorato, Via Verdi 8, Torino

- Giornata del Dottorato di Immunologia e Biologia Cellulare 2012: 14 dicembre 2012; presso l’MBC, Via Nizza 52 Torino.

 

DOCUMENTAZIONE RELATIVA ALLA PARTECIPAZIONE AD ATTIVITA’ FORMATIVE NELL’ANNO 2011 

 - Seminario: Roberto S. Accolla e Giovanna Tosi “Intrinsic and adaptive immunity: the dual function CIITA as viral  restriction factor and as inducer of specific immunity against tumors”, 16 Marzo 2011; presso l’MBC, Via Nizza 52 Torino

 - Seminario: Prof. Federico Garrido “The escape of cancer from immune surveillance: MHC expression and tumor rejection”, 21 marzo 2011; presso l'MBC, Via Nizza 52 Torino

- Corso: Prof. Guido Forni “Corso Monografico sull'Immunologia dei Tumori”in sei lezioni (10 maggio 2011, 17 maggio 2011, 24 maggio 2011, 31 maggio 2011, 7 giugno 2011, 14 giugno 2011); presso Ospedale San Luigi, Orbassano.

- Workshop: “The Biology of Cancer Oncogene and Microenviroment” organizzato dalla Fondazione Piemontese per la Ricerca sul Cancro –ONLUS, 29 maggio 2011 a Torino.

- Corso: Prof. Caselle “Ricerca Bibliografica e Database” (due lezioni teoriche e due esercitazioni al pc) presso il Dipartimento di Fisica, via Pietro Giuria 1, Torino:

  “La ricerca bibliografica in Pubmed” 12 settembre 2011

  “La ricerca bibliografica nelle banche dati citazionali” 13 settembre 2011

  “Esercitazione - Pubmed” 22 settembre 2011

  “Esercitazione – Isi-Wos e Scopus” 28 settembre 2011

 - Seminario: Pier Paolo Pandolfi MD, PhD “The ceRNA hypothesis and the non-coding revolution in cancer research  and therapy” 14 settembre 2011; presso l’MBC, Via Nizza 52 Torino.

 - D-Day, 19 settembre 2011 organizzato dalla Scuola di Dottorato in Scienze della Vita e della Salute, presso l’MBC, Via Nizza 52 Torino

- Incontro: "la ricerca?...Che impresa! - Opportunità e percorsi per valorizzare la Ricerca e favorire il Trasferimento Tecnologico" organizzato da 2i3T, Società per la Gestione dell'Incubatore d'Impresa ed il Trasferimento Tecnologico dell'Università di Torino; 29 settembre 2011; presso l'MBC, Via Nizza 52 Torino

 - Seminario: Prof. Mariano Barbacid “Mouse Models of Cancer: A Genetic Tool to Validate Therapeutic Targets”, 19 Ottobre 2011; presso l’MBC, Via Nizza 52 Torino.

 - Seminario: Dott.ssa Elena Giglia “Open Access, i vantaggi per chi fa ricerca”, 30 novembre 2011, presso il Dipartimento di Patologia Generale

 - Giornata del Dottorato di Immunologia e Biologia Cellulare 2011: 14 dicembre 2011; presso l’MBC, Via Nizza 52 Torino.

 

DOCUMENTAZIONE RELATIVA ALLA PARTECIPAZIONE AD ATTIVITA’ FORMATIVE NELL’ANNO 2012

- Magistral Lecture: James Dewey Watson, Nobel Prize Cold Spring Harbor Laboratory - USA "Must most metastatic cancer remain "incurable"?", 11 Ottobre, IRCC, Candiolo

 

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