et al

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T
TH HÈ ÈS SE E
En vue de l'obtention du
D
DO OC CT TO OR RA AT T D DE E L L’ ’U UN NI IV VE ER RS SI IT TÉ É D DE E T TO OU UL LO OU US SE E
Délivré par l’Université Toulouse III – Paul Sabatier
Discipline ou spécialité : Cancérologie
JURY
Pr Thierry LEVADE, Professeur des Universités Président
Dr Fabienne FOUFELLE, Directeur de Recherche, INSERM Rapporteur
Dr Frederic BOST, Directeur de Recherche, CNRS Rapporteur
Pr Charles DUMONTET, Professeur des Universités Rapporteur
Pr Guo-sheng Ren, Professeur de l`Universités Medicale de Chongqing Invités
Pr Catherine Muller, Professeur des Universités Directeur de thèse
Pr Philippe Valet, Professeur des Universités Directeur de thèse
Ecole doctorale : Ecole doctorale Biologie Santé Biotechnologies
Unité de recherche : IPBS CNRS UMR5089
Directeurs de Thèse : Pr Catherine Muller et Pr Philippe Valet
Rapporteurs: Fabienne FOUFELLE, Frederic BOST, Charles DUMONTET
Présentée et soutenue par Yuan Yuan WANG
Le 25 September 2013
Titre : Deciphering the crosstalk between breast cancer cells and tumour-surrounding
adipocytes : contribution of cell metabolic symbiosis

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Acknowledgment
First and foremost, I would like to express the deepest appreciation to my “science parents”: Prof.
Catherine Muller and Prof. Philippe Valet for inspiring me and for providing such an interesting
project for me to work during these four years. Thank you for your direction and your help in the
development of my scientific mind: innovative concept, insistence, enthusiasm, strict for the
science, and how to give a speech in front of people. I am honored to have worked with you and I
have learned more from you than you will know.
Thanks to the past members in MIKA team: thanks to Bea not only for teaching me many
experiment skills from my very beginning and start this interesting project, but also teaching me
how to make crêpe and Moelleux a l`ananas et noix de coco, and also all the “useful French words”
. I am really happy to have you such a kind and straight “little boss” and French friend. Thanks to
Lud for picking me at the train station when I first arrived in Toulouse and helping me a lot from
the life to the work at the beginning. Thanks to Cathy Botanch for your welcome cake and your
kindness.
Thanks to the present members in our team, you are really helpful and friendly: Steph for teaching
me how to use confocal microscopy and all the IF analysis; Laurence, for reviewing my thesis
manuscript in spite of your very busy schedule and I am enjoying discussing with you; The
“Prostate boys”: Victor and Adrien, the rest “Breast girls” Camille Lehood, hey chouette! and
Delphine, “Melanoma princess” Ikrame and “Hypoxia queen” Fred, Your lively discussion at group
meeting have made science come to life, I have truly valued our scientific interaction. I treasure all
the fun we have made during these years and each time we got together, running, eating and
drinking… and you are also very good French teacher “Ca roule ma poule” “c’est parti mon kiki” I
will frequently repeat them in order to keep link with you 
Thanks to “Adipolab” members: especially, “Mice queen” Sophie for helping and teaching me the
in vivo experiment, Camille for the β-oxidation detection and Cedric for providing me several
antibodies.
Thanks to Madama Escourrou Ghislaine for all Immunohistochemistry analysis and I learnt a lot
about “the microcosmic world” of breast cancer.
Thanks to other person in IPBS: Leyre, Guillaume, Piere, Emma, Ying, Jin, Zhong, Jiahui for you
kind help.
Thanks to my thesis committee members: for your encouragement, insightful comments and hard
questions.
I would like to acknowledge the financial support from CSC for 4 years that made my Ph.D work
possible.
I have been fortunate to come across many funny and good Chinese friends: SuSu, Liang, Tian,
Xiaoqian, Jian, Hang, Han, Lijun,Mingchun et al. without you, life would be bleak. Thanks for the
movies, dinners, sports, concerts and plays we enjoy together.
My sincere thanks also go to Prof. Ren GuoSheng, for offering me this opportunity to study abroad.
Lastly, I am profoundly thankful for the love, support and understanding from my parents, my
grandma!
Thank Toulouse! This sunny, lovely and peaceful city! Thank all of you!

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Abbreviation
ACC
ACL
ACS
ADF
ADRP
ADSCs
ANLS
AMPK
ANP
APC
AOX
AT
ATGL
ARF
BMP7
BMAT
BNP
CAA
CAC
CAF
CACT
C/EBP
CNP
CK1
CLS
COLVI
CPT
CSF-1
CGI-58
DFAT
DC
DGAT
DG
DLBCL
EGF
ER
ECM
EMT
FABP
FAP
FAS
FFA
FGF
FN
FSP-1
Acetyl CoA carboxylase
ATP citrate lyase
Acyl-CoA synthase
Adipocyte-Derived Fibroblast
Adipocyte differentiation-related protein
Adipocyte-Derived Stem cells
Astrocyte-neuron shuttle
AMP Activated Protein Kinase
Atrial natriuretic peptide
Adenomatous Polyposis Coli
Acyl-CoA oxidase
Adipose tissue
Adipocyte Triglyceride Lipase
ADP-ribosylation factor
Bone morphogenetic protein 7
Bone marrow adipose tissue
Brain natriuretic peptide
Cancer-Associated Adipocyte
Cancer associated cachexia
Cancer-Associated Fibroblast
Carnitine acylcarnitine translocase
CAAT/Enhancer Binding Protein
C-type natriuretic peptide
Casein Kinase 1
Crown like structure
Collagen VI
Carnitine palmitoyltransferase
Macrophage Colony-Stimulating Factor-1
Comparative gene identification-58
Dedifferentiated Fat Cell
Dendritic Cell
Diacylglycerol acyltransferase
Diacylglycerol
Diffuse large B cell lymphoma
Epidermal Growth Factor
Estrogen receptor
Extracellular matrix
epithelial-to-mesenchymal transition
Fatty acid binding protein
Fibroblast Activated Protein
Fatty Acid Synthase
Free fatty acid
Fibroblast Growth Factor
Fibronectine
Fibroblast-Specific Protein-1

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GSK-3β
HDAC-1
HER2/neu
HFD
HGF
HIF
HSL
IFN
IGF-1
iNOS
IL
IMC
KLF
KG
LD
LDH-A
LEF/TCF
LCAD
LHYD
LKAT
LRP
MAGL
MAPK
MAT
MCP
MEC
MMP
MIC-1
MUFA
mTOR
NG2
NK
NPR
OB-R
PAI1
PDGF
PI3K
PPAR
PGC1α
PLD
PKA
PDH
PDK
Glycogene Synthase Kinase-3β
Histone deacetylase-1
Human epidermal growth factor receptor 2
High fat diet
Hepatocyte Growth Factor
Hypoxia-inducible factor
Hormone sensitive lipase
Interferon
Insuline-like Growth Factor-1
Inducible nitric oxide synthase
Interleukine
Indice de masse corporelle
Kruppel-Like zinc finger transcription Factor
Ketoglutarate
Lipid droplet
Lactate dehydrogenase A
Lymphoid-Enhancer-binding Factor/T-Cell-specific transcription Factor
Long chain acyl-CoA dehydrogenase
Long chain enoyl-CoA hydratase
Long chain 3-ketoacyl-CoA thiolase
Low-density lipoprotein Receptor-related protein
MonoAcylGlycerol Lipase
Mitogen Activated Protein Kinase
Mammary adipose tissue
Monocyte Chemoattractant Protein
Matrice Extra-Cellulaire
Matrix MetalloProtease
Macrophage inhibitory cytokine 1
Monounsaturated fatty acid
Mammalian target of rapamycin
Neuron-Glial Antigen-2
Natural Killer
Natriuretic peptide receptor
Leptin receptor
Plasminogen activator inhibitor 1
Platelet-Derived Growth Factor
PhosphoInositol-3-kinase
Peroxisome Proliferator Activated Receptor
PPARγ co-activator 1α
Phospholipase D
Protein kinase A
Pyruvate dehydrogenase
Pyruvate dehydrogenase kinase enzyme

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PML
ROS
SAT
SCO2
SCD
S1P
SHBG
αSMA
SREBP
STAT
SETDB1
SVF
TADC
TAM
TCF
TEC
TAG
TGF
TNC
TNF
TFP
TIP47
TIGAR
TLR4
UCP1
USP2a
VAT
VEGF
Wnt
Promyelocytic leukaemia
Reactive oxygen species
Subcutaneous adipose tissue
Synthesis of cytochrome C oxidase protein
Stearoyl-CoA desaturase
Sphingosine 1-Phosphate
Sex Hormone Binding Globulin
α-Smooth Muscle Actin
Sterol Regulatory Element Binding Protein
Signal Transducer and activators of transcription
SET domain bifurcated 1
Stroma vascular fraction
Tumor Associated Dendritic Cell
Tumor Associated Macrophage
T cell-specific transcription factor
Tumor Associated endothelial cell
Triacylglycerol
Transforming Growth Factor
Tenascine-c
Tumor Necrosis Factor
Trifunctional protein
Tail-interacting protein of 47kDa
TP53-Induced Glycolysis and Apoptosis Regulator
Toll like receptor
Uncoupling protein 1
Ubiquitin-specific protease 2a
Visceral adipose tissue
Vascular Endothelium Growth Factor
Wingless-type MMTV integration site