Cherdyntseva, Nadezhda V.

Gerashchenko, Tatiana S.

Krakhmal, Nadezhda V.

Novikov, Nikita

Perelmuter, Vladimir M.

Tashireva, Lubov A.

Zavyalova, Marina V.

English

Tomsk State University Repository

Posters Session 1 Cancer Cell Plasticity74     3rd International Cancer Symposium of the Cancer Research Center of LyonCANCER CELL PLASTICITYmorphological structures differed from each in the number of expressed genes of the epithelial and mesenchymal phenotypes and the association with cancer invasion pathways. Tubular, alveolar, and solid structures were characterized by the same proportion of epithelial and mesenchymal genes; however, solid patterns of tumor cells demonstrated protrusions of collectively invading cells with loss or overexpression of certain proteins involved in the realization of cancer invasion program. Trabecular and discrete groups of tumor cells showed a dramatic %)40)&3)( +$( /1)( )>;0)33+#$( #.( );+/1)7+&7( ,)$)3-( &( 3+,$+24&$/( +$40)&3)(in the number of mesenchymal markers and, surprisingly, the highest proliferative activity (as determined by Ki-67 immunostaining). Discrete groups of tumor cells, as well as solid structures, were characterized by /1)(3+,$+24&$/(0),67&/+#$(#.(4'/#3H)7)/&7(%'$&5+43(<'(/1)(_1#(.&5+7'(#.(GTPases. Signaling pathways, which are linked with the activity of matrix metalloproteases, transendothelial migration, and cancer invasion in ,)$)0&7-(:)0)(3+,$+24&$/7'(&33#4+&/)%(:+/1(%+340)/)(,0#6;3(#.(/65#0(4)773(and tended to be related to trabecular structures.Conclusions: Different morphological structures in BC represent transcriptionally distinct tumor cell subpopulations with varied degree of epithelial-mesenchymal transition and invasion. Overall, intratumor morphological heterogeneity in BC represents a promising model for the study of cancer invasion.The study was supported by Russian Science Foundation Grant (#14-15-00318).P 01 - 018SINGLE CELL GENOMIC ANALYSIS PIPELINE USING DEPARRAY TECHNOLOGY: AN APPLICATION TO STUDY CIRCULATING TUMOR CELL SUB-POPULATIONSCatherine Rey1, Séverine Croze1, Magali Roche2, Adriana Plesa6, Anne Wierinckx1,3,4, Catherine Legras-Lachuer2,3,5, Charles Dumontet1,3,4,6, Joel Lachuer1,3,4 (presenting author)1!"#$%&'()'#*+!,-./01*+!23.,!45./,6786!/!93,0.5!4,:+!;<$=+!-#>=?'@!2 ViroScan3D, TREVOUX, F-01600, France; 3 Université de Lyon, Université Lyon 1, Lyon, France; 4 Centre de Recherche en Cancérologie de Lyon, INSERM U1052/CNRS UMR 5286 Centre Léon Bérard, Lyon, France; 5 UMR CNRS 5557 UCBL USC INRA 1193 ENVL, Dynamique microbienne et transmission virale, Lyon, France; 6 UMR 1052-CNRS 5286, INSERM/CRCL-Anticorps Anticancer Faculté de Médecine Rockefeller, F-69008 Lyon, FranceKeywords: single-cell, genomics, DEParray, Tumor cells heterogeneity, CTCHigh-throughput Genomics analysis at single cell level resolution is a major revolution to understand molecular mechanisms occurring in heterogeneous tissues. These approaches allow us to decipher genetics portrait of cell subpopulations including rare cells present in physiological or pathological tissues (as stem cells or other underrepresented cells) or in blood (as rare CTC). Different technologies coupling unique cell sorting BDL( 3+$,7)( 4)77( &6/#;0);( 3'3/)5( .0#5( Z6+%+,5-( =?D`-( ADC^^O( .0#5(9&.)0,)$-(410#5+65(3+$,7)(4)77(.0#5(LKh(,)$#5+43()/4zE(:+/1(GI?V_I?(&5;7+24&/+#$(.#77#:)%(<'(WD_(#0(I):(Y)$)0&/+#$(`)[6)$4+$,(&$&7'3+3(permit to reach genetics/transcriptomics and epigenetics knowledge at single cell level. However none of these technologies permit to associate cell phenotypic features such as size, shape, presence or absence of one or more target surface proteins and genetics features. The technology 4&77)%(GCW?00&'( /)41$#7#,'( B`+7+4#$(d+#3'3/)53E(&77#:3(;60+24&/+#$(#.(multiple different types of cells (by group of cells or at single cell level) .0#5(&(3+$,7)(3&5;7)(+%)$/+2)%(<'(4#5<+$&/+#$3(#.(567/+;7)(+$/0&4)7767&0(and extracellular markers, as well as with the use of morphological features such as circularity or size. This technology permits the isolation of rare cells subpopulations coming from fresh culture, or Circulating Tumour Cells (CTC) (Molecular analysis of circulating tumor cells +%)$/+2)3(%+3/+$4/( 4#;'@$65<)0(;0#27)3( +$( ;&/+)$/3(:+/1( 41)5#3)$3+/+*)(and chemorefractory small-cell lung cancer. Carter L et al, Nat Med. 2016 Nov) but also from FFPE tissues (Digital Sorting of Pure Cell Populations Enables Unambiguous Genetic Analysis of Heterogeneous Formalin-=+>)%( W&0&.2$@C5<)%%)%( F65#03( <'( I)>/( Y)$)0&/+#$( `)[6)$4+$,8(Bolognesi C et al, Sci Rep. 2016 Feb).   W0#27)h;)0/-( /1)(,)$#5+43(&$%(5+40#,)$#5+43(;7&/.#05(#.( /1)(_1k$)@P 01 - 016INTERPLAY BETWEEN GABA METABOLISM AND EPIGENETIC REGULATION IN THE CONTROL OF GLIOMA CELL PROPERTIESElias A. El-Habr1 (presenting author), Luiz G. Dubois2, Fanny Burel-Vandenbos3, Alexandra Bogeas1, Laurent Turchi3, François-Xavier Lejeune1, Bryan M. Wittmann4, Mohamed Fareh3, Emna Mahfoudhi5, Maxime Janin6, Ashwin Narayanan1, Ghislaine Morvan-Dubois1, Charlotte Schmitt7, Lisa Oliver8, Chris Ottolenghi6, Isabelle Plo5, Vivaldo Moura-Neto2, Thierry Virolle3, Hervé Chneiweiss1, Marie-Pierre Junier11 CNRS UMR8246, Inserm U1130, UPMC, Neuroscience Paris Seine-IBPS, Sorbonne Universities Paris France; 2 Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria de Estado de Saúde do Rio de Janeiro/RJRio De Janeiro Brazil; 3 Université de Nice-Sophia Antipolis, Institut de Biologie Valrose, CNRS UMR 7277, Inserm U1091 Nice France; 4 Metabolon, Inc. Durham USA; 5 Inserm U1009 Institut Gustave Roussy Villejuif France; 6 Department of Biochemistry University Paris Descartes, Hospital Necker Enfants Malades Paris France; 7 Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM Paris France; 8 Team 9 CRCNA, UMR 892 Inserm, 6299 CNRS Université de Nantes, Nantes Cedex 07 FranceKeywords: Brain cancer , DIPG, Cancer stem cell , ALDH5A1, 5-hmCCell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic 41&$,)3( +$(4)77( 3/&/)3( +3(6$H$#:$8(")/&<#7+/)(;0#27+$,(#.(165&$(&%67/(glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4 hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying 5#7)467&0( ;0#27)3-( &7#$,( :+/1( 4)773( .0#5( ;)%+&/0+4( ;#$/+$)( ,7+#5&38( A$(&77(4)77( /';)3-(Yfd(&4/)%(<'( +$1+<+/+$,(!@H)/#,76/&0&/)@%);)$%)$/(F)$leleven Translocations (TET) activity, resulting in decreased levels of the 5-hydroxymethylcytosine epigenetic mark. In patients, low SSADH )>;0)33+#$( :&3( 4#00)7&/)%( :+/1( 1+,1( YfdV!@H)/#,76/&0&/)( 0&/+#3-( &$%(distinguished weakly proliferative/ differentiated glioblastoma territories .0#5( ;0#7+.)0&/+*)V$#$@%+..)0)$/+&/)%( /)00+/#0+)38( g60( 2$%+$,3( 36;;#0/(an active participation of metabolic variations in the genesis of tumor heterogeneity.El-Habr et al., Acta Neuropathol. 2017 Apr;133(4):645-660P 01 - 017INTRATUMOR MORPHOLOGICAL HETEROGENEITY IN BREAST CANCER AS A MODEL FOR THE STUDY OF CANCER INVASIONTatiana Gerashchenko1,2, Lyubov Tashireva1, Nikita Novikov2, Nadezhda Krakhmal1,3, Marina Zavyalova1,2,3, Nadezhda Cherdyntseva1,2, Vladimir Perelmuter11 Tomsk National Research Medical Center, Tomsk, Russia; 2 Tomsk State University, Tomsk, Russia; 3 Siberian State Medical University, Tomsk, RussiaKeywords: breast cancer, tumor heterogeneity, cancer invasion, epithelial-mesenchymal transitionBackground: Different architectural arrangements of tumor cells within the primary tumor named as histological or morphological structures probably 0)Z)4/( 3;)4+24( 4&$4)0( +$*&3+#$( ;&//)0$38( A$( /1+3( 3/6%'-( :)( .#463)%( #$(the intratumor morphological heterogeneity in breast cancer (BC) and analyzed whether morphologically distinct structures (tubular, alveolar, solid, trabecular and discrete) demonstrate invasive characteristics.Material and methods: Fifty BC patients (T1-4N0-3M0-1) were included in this study. Laser microdissection-assisted gene expression microarrays :)0)( &;;7+)%( /#( ;)0.#05( /0&$340+;/#5)( ;0#27+$,( #.( 5#0;1#7#,+4&7(structures. Immunohistochemistry analysis was used for validation of proteins differentially expressed in morphological structures._)367/3T( C&41( /';)( #.( 5#0;1#7#,+4&7( 3/064/60)3( %)5#$3/0&/)%( 3;)4+24(,)$)( )>;0)33+#$( ;0#27)3( &$%( 3+,$&7+$,( ;&/1:&'38( "#3/( +5;#0/&$/7'-(

Intratumor morphological heterogeneity in breast cancer as a model for the study of cancer invasion

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Intratumor morphological heterogeneity in breast cancer as a model for the study of cancer invasion

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