ORBi: Turtoi Andrei - INTRA-TUMORAL HETEROGENEITY AND RATIONAL SELECTION OF ANTIGENS FOR TARGETED THERAPY OF LIVER METASTASES

Reference : INTRA-TUMORAL HETEROGENEITY AND RATIONAL SELECTION OF ANTIGENS FOR TARGETED THERAPY OF L...


	Document type :	Scientific congresses and symposiums : Paper published in a journal
	Discipline(s) :	Human health sciences : Surgery
	To cite this reference:	http://hdl.handle.net/2268/126046

Title :	INTRA-TUMORAL HETEROGENEITY AND RATIONAL SELECTION OF ANTIGENS FOR TARGETED THERAPY OF LIVER METASTASES
Language :	English
Author, co-author :	Turtoi, Andrei [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
	Blomme, Arnaud [Université de Liège - ULg > > > Form. doc. sc. bioméd. & pharma.]
	Delvaux, David [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
	Dumont, Bruno [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
	SOMJA, Joan [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
	Debois, Delphine [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
	DELVENNE, Philippe [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
	De Pauw, Edwin [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
	DE ROOVER, Arnaud [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie abdominale- endocrinienne et de transplantation >]
	Honoré, Pierre [Université de Liège - ULg > Département des sciences cliniques > Chirurgicale abdominale >]
	DETRY, Olivier [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie abdominale- endocrinienne et de transplantation >]
	Castronovo, Vincenzo [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
Publication date :	May-2012
Journal title :	Acta Chirurgica Belgica
Publisher :	Acta Medica Belgica
Volume :	112
Issue/season :	3
Pages :	89.FP53.
On invitation :	No
Audience :	National
ISSN :	0001-5458
City :	Bruxelles
Country :	Belgique
Event name :	Thirteenth Belgian Surgical Week
Event date :	du 9 au 12 mai 2012
Event organizer :	Royal Belgian Society for Surgery
Event place (city) :	Spa
Event country :	Belgium
Abstract :	[en] Objectives: Targeted therapies of liver metastases are gaining a major stake in current and future treatment options. However, the malignant lesions are heterogeneous in nature offering niches for cancer cells causing treatment resistance and relapse. Therefore, a rational strategy is needed to select targetable antigens that would overcome this intra-tumoral heterogeneity. Methods: After ethical committee approval, 48 fresh liver metastases of colorectal origin were prospectively collected from patients undergoing liver resection. Here we macroscopically divided the lesion in different zones and generated a unique quantitative picture of the proteome heterogeneity in colorectal carcinoma liver metastases. Particular focus was laid on accessible proteins, a protein subclass comprising cell membrane associated and extracellular proteins. Accordingly, the tissues were ex-vivo biotinylated, affinity purified and analyzed for each zone separately using nano-UPLC-MSe proteomics technique. In total over 1500 unique proteins were statistically divided into different patterns of expression. Results: We have generated a quantitative picture of the proteome heterogeneity in colorectal carcinoma liver metastases. The study offers insight into novel targets but also antigens against which the antibodies are already involved in clinical trials or treatment of liver metastases. Extensive clustering and validation experiments highlight novel markers that offer the potential to homogeneously cover the metastatic lesion and become better targets. Conclusions: Two such antigens, LTBP2 and TGFBI were selected for functional analysis in colorectal carcinoma cells. In vitro and in vivo experiments showed that in particular TGFBI is relevant for migration and proliferation capacity of colorectal cancer cells. The suppression of this protein led to significant inhibition of tumor growth, crystalizing it as bona fide target for the development of anti-metastases therapies.
Permalink :	http://hdl.handle.net/2268/126046

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