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Jiyoung Park, Philipp E. Scherer
Published October 8, 2012
Citation Information: J Clin Invest. 2012;122(11):4243-4256. https://doi.org/10.1172/JCI63930.
Citation Information: J Clin Invest. 2012;122(11):4243-4256. https://doi.org/10.1172/JCI63930.
Abstract
Adipocytes represent a major cell type in the mammary tumor microenvironment and are important for tumor growth. Collagen VI (COL6) is highly expressed in adipose tissue, upregulated in the obese state, and enriched in breast cancer lesions and is a stimulator of mammary tumor growth. Here, we have described a cleavage product of the COL6α3 chain, endotrophin (ETP), which serves as the major mediator of the COL6-mediated tumor effects. ETP augmented fibrosis, angiogenesis, and inflammation through recruitment of macrophages and endothelial cells. Moreover, ETP expression was associated with aggressive mammary tumor growth and high metastatic growth. These effects were partially mediated through enhanced TGF-β signaling, which contributes to tissue fibrosis and epithelial-mesenchymal transition (EMT) of tumor cells. Our results highlight the crucial role of ETP as an obesity-associated factor that promotes tumor growth in the context of adipocyte interactions with tumor and stromal cells.
Authors
Jiyoung Park, Philipp E. Scherer
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Citation information
Citations to this article (186)
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Frontiers in Endocrinology | 2019 |
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Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication
JB Funcke, PE Scherer |
Journal of lipid research | 2019 |
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The role of extracellular matrix in mouse and human corneal neovascularization
M Barbariga, F Vallone, E Mosca, F Bignami, C Magagnotti, P Fonteyne, F Chiappori, L Milanesi, P Rama, A Andolfo, G Ferrari |
Scientific Reports | 2019 |
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Mechanochemical Signaling of the Extracellular Matrix in Epithelial-Mesenchymal Transition
LE Scott, SH Weinberg, CA Lemmon |
Frontiers in Cell and Developmental Biology | 2019 |
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Collagen turnover profiles in chronic kidney disease
DG Rasmussen, L Boesby, SH Nielsen, M Tepel, S Birot, MA Karsdal, AL Kamper, F Genovese |
Scientific Reports | 2019 |
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Remodeling of Murine Mammary Adipose Tissue during Pregnancy, Lactation, and Involution
QA Wang, PE Scherer |
Journal of Mammary Gland Biology and Neoplasia | 2019 |
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Decreased collagen VI in the tunica media of pulmonary vessels during exposure to hypoxia: a novel step in pulmonary arterial remodeling
M Žaloudíková, A Eckhardt, R Vytášek, J Uhlík, T Novotný, L Bačáková, J Musílková, V Hampl |
Pulmonary circulation | 2019 |
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Adipocytes promote breast cancer resistance to chemotherapy, a process amplified by obesity: role of the major vault protein (MVP)
C Lehuédé, X Li, S Dauvillier, C Vaysse, C Franchet, E Clement, D Esteve, M Longué, L Chaltiel, SL Gonidec, I Lazar, A Geneste, C Dumontet, P Valet, L Nieto, F Fallone, C Muller |
Breast Cancer Research | 2019 |
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C-terminal proteolysis of the collagen VI α3 chain by BMP-1 and proprotein convertase(s) releases endotrophin in fragments of different sizes
SE Heumüller, M Talantikite, M Napoli, J Armengaud, M Mörgelin, U Hartmann, G Sengle, M Paulsson, C Moali, R Wagener |
The Journal of biological chemistry | 2019 |
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Gene Expression Profiling of the Extracellular Matrix Signature in Macrophages of Different Activation Status: Relevance for Skin Wound Healing
J Etich, M Koch, R Wagener, F Zaucke, M Fabri, B Brachvogel |
International journal of molecular sciences | 2019 |
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Fat fibrosis: friend or foe?
Ritwik Datta, Michael Podolsky, Kamran Atabai |
JCI Insight | 2018 |
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Adipocyte-derived IL-6 and leptin promote breast Cancer metastasis via upregulation of Lysyl Hydroxylase-2 expression
JY He, XH Wei, SJ Li, Y Liu, HL Hu, ZZ Li, XH Kuang, L Wang, X Shi, ST Yuan, L Sun |
Cell Communication and Signaling | 2018 |
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The Role of the Extracellular Matrix and Its Molecular and Cellular Regulators in Cancer Cell Plasticity
V Poltavets, M Kochetkova, SM Pitson, MS Samuel |
Frontiers in Oncology | 2018 |
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Stromal collagen type VI associates with features of malignancy and predicts poor prognosis in salivary gland cancer
L Angenendt, JH Mikesch, D Görlich, A Busch, I Arnhold, C Rudack, W Hartmann, E Wardelmann, WE Berdel, M Stenner, C Schliemann, I Grünewald |
Cellular Oncology | 2018 |
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Seneca Valley Virus Exploits TEM8, a Collagen Receptor Implicated in Tumor Growth
DJ Evans, AM Wasinger, RN Brey, JM Dunleavey, BS Croix, JG Bann |
Frontiers in Oncology | 2018 |
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Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis
Y Hasegawa, K Ikeda, Y Chen, DL Alba, D Stifler, K Shinoda, T Hosono, P Maretich, Y Yang, Y Ishigaki, J Chi, P Cohen, SK Koliwad, S Kajimura |
Cell Metabolism | 2018 |
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Emerging nonmetabolic functions of skin fat
CF Guerrero-Juarez, MV Plikus |
Nature Reviews Endocrinology | 2018 |
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Mutual concessions and compromises between stromal cells and cancer cells: driving tumor development and drug resistance
P Nilendu, SC Sarode, D Jahagirdar, I Tandon, S Patil, GS Sarode, JK Pal, NK Sharma |
Cellular Oncology | 2018 |
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Role of COL6A3 in colorectal cancer
W Liu, L Li, H Ye, H Tao, H He |
Oncology reports | 2018 |
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The Ominous Triad of Adipose Tissue Dysfunction:
Inflammation, Fibrosis and Angiogenesis
Clair Crewe, Yu Aaron An, Philipp E. Scherer |
Journal of Clinical Investigation | 2017 |
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Inflammation of mammary adipose tissue occurs in overweight and obese patients exhibiting early-stage breast cancer
C Vaysse, J Lømo, Ø Garred, F Fjeldheim, T Lofteroed, E Schlichting, A McTiernan, H Frydenberg, A Husøy, S Lundgren, MW Fagerland, E Richardsen, EA Wist, C Muller, I Thune |
npj Breast Cancer | 2017 |
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The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance
MN Duong, A Geneste, F Fallone, X Li, C Dumontet, C Muller |
Oncotarget | 2017 |
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An atlas of bloodstream-accessible bone marrow proteins for site-directed therapy of acute myeloid leukemia
L Angenendt, S Reuter, D Kentrup, AS Benk, F Neumann, J Hüve, AC Martens, C Schwöppe, T Kessler, LH Schmidt, T Sauer, C Brand, JH Mikesch, G Lenz, RM Mesters, C Müller-Tidow, W Hartmann, E Wardelmann, D Neri, WE Berdel, C Roesli, C Schliemann |
Leukemia | 2017 |
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Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD
AR Bihlet, MA Karsdal, JM Sand, DJ Leeming, M Roberts, W White, R Bowler |
Respiratory Research | 2017 |
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Serum endotrophin, a type VI collagen cleavage product, is associated with increased mortality in chronic kidney disease
A Fenton, MD Jesky, CJ Ferro, J Sørensen, MA Karsdal, P Cockwell, F Genovese, AI Aguilera |
PloS one | 2017 |
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Urinary endotrophin predicts disease progression in patients with chronic kidney disease
DG Rasmussen, A Fenton, M Jesky, C Ferro, P Boor, M Tepel, MA Karsdal, F Genovese, P Cockwell |
Scientific Reports | 2017 |
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Transcriptome profiling identifies regulators of pathogenesis in collagen VI related muscular dystrophy
RJ Butterfield, DM Dunn, Y Hu, K Johnson, CG Bönnemann, RB Weiss, F Ruggiero |
PloS one | 2017 |
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Local effects of adipose tissue in psoriasis and psoriatic arthritis
I Kruglikov, U Wollina |
Psoriasis: Targets and Therapy | 2017 |
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Divergent functions of endotrophin on different cell populations in adipose tissue
Y Zhao, X Gu, N Zhang, MG Kolonin, Z An, K Sun |
American journal of physiology. Endocrinology and metabolism | 2016 |
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Microenvironmental Control of Adipocyte Fate and Function
BD Pope, CR Warren, KK Parker, CA Cowan |
Trends in Cell Biology | 2016 |
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Targeting adipose tissue in the treatment of obesity-associated diabetes
CM Kusminski, PE Bickel, PE Scherer |
Nature Reviews Drug Discovery | 2016 |
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Mesenchymal stem cells as a double-edged sword in suppression or progression of solid tumor cells
F Norozi, A Ahmadzadeh, S Shahrabi, T Vosoughi, N Saki |
Tumor Biology | 2016 |
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The Multifaceted Roles of Adipose Tissue—Therapeutic Targets for Diabetes and Beyond: The 2015 Banting Lecture
PE Scherer |
Diabetes | 2016 |
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Epithelial–mesenchymal transition: a new target in anticancer drug discovery
F Marcucci, G Stassi, RD Maria |
Nature Reviews Drug Discovery | 2016 |
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Obesity and colorectal cancer: molecular features of adipose tissue
J Martinez-Useros, J Garcia-Foncillas |
Journal of Translational Medicine | 2016 |
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Identification and Characterization of Novel Matrix-Derived Bioactive Peptides: A Role for Collagenase from Santyl® Ointment in Post-Debridement Wound Healing?
AR Sheets, TN Demidova-Rice, L Shi, V Ronfard, KV Grover, IM Herman, CJ Connon |
PloS one | 2016 |
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Endotrophin, a multifaceted player in metabolic dysregulation and cancer progression, is a predictive biomarker for the response to PPARγ agonist treatment
K Sun, J Park, M Kim, PE Scherer |
Diabetologia | 2016 |
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Dietary restriction: could it be considered as speed bump on tumor progression road?
A Cangemi, D Fanale, G Rinaldi, V Bazan, A Galvano, A Perez, N Barraco, D Massihnia, M Castiglia, S Vieni, G Bronte, M Mirisola, A Russo |
Tumor Biology | 2016 |
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Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes
MA Karsdal, K Henriksen, F Genovese, DJ Leeming, MJ Nielsen, BJ Riis, C Christiansen, I Byrjalsen, D Schuppan |
Diabetologia | 2016 |
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Clinical significance of serum omentin-1 levels in patients with pancreatic adenocarcinoma
S Karabulut, CU Afsar, M Karabulut, H Alis, MA Bozkurt, F Aydogan, M Serilmez, F Tas |
BBA Clinical | 2016 |
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Tumor macrophages are pivotal constructors of tumor collagenous matrix
R Afik, E Zigmond, M Vugman, M Klepfish, E Shimshoni, M Pasmanik-Chor, A Shenoy, E Bassat, Z Halpern, T Geiger, I Sagi, C Varol |
Journal of Experimental Medicine | 2016 |
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A High-Fat Diet Promotes Mammary Gland Myofibroblast Differentiation through MicroRNA 140 Downregulation
B Wolfson, Y Zhang, R Gernapudi, N Duru, Y Yao, PK Lo, Q Zhou |
Molecular and cellular biology | 2016 |
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Mammary tissue microenvironment determines T cell-dependent breast cancer-associated inflammation
K Takahashi, N Nagai, K Ogura, K Tsuneyama, I Saiki, T Irimura, Y Hayakawa |
Cancer Science | 2015 |
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Why does obesity promote cancer? Epidemiology, biology, and open questions
L Mazzarella |
ecancermedicalscience | 2015 |
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Bone marrow as a metastatic niche for disseminated tumor cells from solid tumors
Y Shiozawa, MR Eber, JE Berry, RS Taichman |
BoneKEy Reports | 2015 |
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Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis
BR Seo, P Bhardwaj, S Choi, J Gonzalez, RC Eguiluz, K Wang, S Mohanan, PG Morris, B Du, XK Zhou, LT Vahdat, A Verma, O Elemento, CA Hudis, RM Williams, D Gourdon, AJ Dannenberg, C Fischbach |
Science Translational Medicine | 2015 |
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Upregulation of COL6A1 is predictive of poor prognosis in clear cell renal cell carcinoma patients
F Wan, H Wang, Y Shen, H Zhang, G Shi, Y Zhu, B Dai, D Ye |
Oncotarget | 2015 |
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Reactive stroma component COL6A1 is upregulated in castration-resistant prostate cancer and promotes tumor growth.
Zhu YP, Wan FN, Shen YJ, Wang HK, Zhang GM, Ye DW |
Oncotarget | 2015 |
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ER -regulated Lipocalin 2 Expression in Adipose Tissue Links Obesity with Breast Cancer Progression
BG Drew, H Hamidi, Z Zhou, CJ Villanueva, SA Krum, AC Calkin, BW Parks, V Ribas, NY Kalajian, J Phun, P Daraei, HR Christofk, SC Hewitt, KS Korach, P Tontonoz, AJ Lusis, DJ Slamon, SA Hurvitz, AL Hevener |
The Journal of biological chemistry | 2014 |
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Obesity and cancer—mechanisms underlying tumour progression and recurrence
J Park, TS Morley, M Kim, DJ Clegg, PE Scherer |
Nature Reviews Endocrinology | 2014 |
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What We Talk About When We Talk About Fat
ED Rosen, BM Spiegelman |
Cell | 2014 |
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Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction
K Sun, J Park, OT Gupta, WL Holland, P Auerbach, N Zhang, RG Marangoni, SM Nicoloro, MP Czech, J Varga, T Ploug, Z An, PE Scherer |
Nature Communications | 2014 |
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The Role of Adipose Tissue and Obesity in Causing Treatment Resistance of Acute Lymphoblastic Leukemia
X Sheng, SD Mittelman |
Frontiers in Pediatrics | 2014 |
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The Role of Collagens in Peripheral Nerve Myelination and Function
P Chen, M Cescon, P Bonaldo |
Molecular Neurobiology | 2014 |
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Collagen VI and Hyaluronan: The Common Role in Breast Cancer
E Karousou, ML D'Angelo, K Kouvidi, D Vigetti, M Viola, D Nikitovic, GD Luca, A Passi |
BioMed Research International | 2014 |
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The efficacy of probiotics for monosodium glutamate-induced obesity: dietology concerns and opportunities for prevention
OA Savcheniuk, OV Virchenko, TM Falalyeyeva, TV Beregova, LP Babenko, LM Lazarenko, OM Demchenko, RV Bubnov, M Spivak |
The EPMA Journal | 2014 |
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Serum omentin level in patients with prostate cancer
U Uyeturk, H Sarıcı, BK Tekce, M Eroglu, E Kemahlı, U Uyeturk, A Gucuk |
Medical Oncology | 2014 |
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Contributions of adipose tissue architectural and tensile properties toward defining healthy and unhealthy obesity
DE Lackey, DH Burk, MR Ali, R Mostaedi, WH Smith, J Park, PE Scherer, SA Seay, CS McCoin, P Bonaldo, SH Adams |
American journal of physiology. Endocrinology and metabolism | 2013 |
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Adipose tissue and adipocytes support tumorigenesis and metastasis
KM Nieman, IL Romero, BV Houten, E Lengyel |
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2013 |
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Fibrosis and Adipose Tissue Dysfunction
K Sun, J Tordjman, K Clément, PE Scherer |
Cell Metabolism | 2013 |
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Adipocytes: impact on tumor growth and potential sites for therapeutic intervention
S Hefetz-Sela, PE Scherer |
Pharmacology & Therapeutics | 2013 |
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Endotrophin in the tumor stroma: a new therapeutic target for breast cancer?
J Park, PE Scherer |
Expert Review of Anticancer Therapy | 2013 |
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Inhibition of endotrophin, a cleavage product of collagen VI, confers cisplatin sensitivity to tumours
J Park, TS Morley, PE Scherer |
EMBO Molecular Medicine | 2013 |
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Loss of adipocyte specification and necrosis augment tumor-associated inflammation
M Wagner, R Bjerkvig, H Wiig, AC Dudley |
Adipocyte | 2013 |
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Hypothermia Activates Adipose Tissue to Promote Malignant Lung Cancer Progression
G Du, B Zhao, Y Zhang, T Sun, W Liu, J Li, Y Liu, Y Wang, H Li, X Hou |
PloS one | 2013 |
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The expanded collagen VI family: new chains and new questions
J Fitzgerald, P Holden, U Hansen |
Connective Tissue Research | 2013 |
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Link between obesity and cancer
SC Williams |
Proceedings of the National Academy of Sciences | 2013 |
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Mammary Stroma in Development and Carcinogenesis
T Sakakura, Y Suzuki, R Shiurba |
Journal of Mammary Gland Biology and Neoplasia | 2013 |
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COL6A3 protein deficiency in mice leads to muscle and tendon defects similar to human collagen VI congenital muscular dystrophy
TC Pan, RZ Zhang, D Markova, M Arita, Y Zhang, S Bogdanovich, TS Khurana, CG Bönnemann, DE Birk, ML Chu |
The Journal of biological chemistry | 2013 |
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Diet, Obesity, and Cancer Progression: Are Adipocytes the Link?
V Venkateswaran, P Toren, B Mora |
Lipid insights | 2013 |
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Endotrophin - Linking Obesity with Aggressive Tumor Growth
J Park, PE Scherer |
Oncotarget | 2012 |
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Comprehensive Physiology
R Terjung |
Comprehensive Physiology | 2011 |
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Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
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