Skip to main content
. 2022 May 6;247(9):713–733. doi: 10.1177/15353702221087962

Table 2.

Cancer cachexia models and mechanisms.

Cancer type In vitroIn vivo Model Mechanism of action or outcome References
Breast cancer Ex vivo Tissue samples ↑FATP1, CD36, UCP1, p-p38,
↓PPARγ, p-PPARγ		 87
In vitro C2C12 cells treated with exosomes from MCF-7 and MDA-MB-231 cells ↑UCP3, p-p38, exosomal miR-155,
↓PPARγ, p-PPARγ, p-ERK1/2		 87
Ex vivo Tissue samples ↑gelsolin, calponin2, tropomyosin 2, vimentin, P4HAI, PKM2
annexin A1, annexin A2, ARHGDIB, PGK1, LDHA, ALDOA, GPD2, ENO1, TPI1, PGAM1, EEF1D, PRDX1, CAT, tenascin C,
SPARC, COL1A1, COL1A2, alpha fetoprotein, metastasis
tumor recurrence,
↓Cav-1, survival		 88
In vitro Cav-1 deficient fibroblasts ↑PKM2, LDHA, reactive oxygen species 88
In vitro MCF-7 ↑leptin, mitochondrial respiration, PYC, G6PD, cell proliferation 89
Colorectal cancer In vitro H9c2 cells ↑Oxidative stress
↓Basal, maximum and spare respiration, ATP, mitochondrial membrane potential and volume		 90
In vivo Mouse cachexia model ↑4-HNE
↓cardiac weight, myocardial area, ATP, SDS-MYL1		 90
Ex vivo Plasma ↑exosomes 91
In vitro Exosomes from CT26 ↑IL-6, atrogin-1, MURF1, myotube atrophy, ↓myotube diameters 91
In vitro C2C12 myoblasts ↑IL-6, atrogin-1 92
In vivo ApcMin/+ mouse ↑IL-6, atrogin-1, gastrocnemius muscle wasting 14
In vivo C26 mouse model ↑LIF, STAT3, p-STAT3, atrophy of myotubes 14
In vivo C26, ApcMin mouse model ↑IL-6, STAT3, p-STAT3, atrophy of muscle fiber 92
In vivo ApcMin mouse model ↑IL-6, p-AMPK, ↓ mTOR 93
In vivo C26 mouse model ↑LC3bII/LC3BI, p62, muscle atrophy 94
In vivo C26 mouse model ↑Pax7, p65, delayed muscle regeneration 95
In vivo C26 mouse model ↑UCP1, PBE, CPT1α, BAT temperature 96
In vitro 3T3-L1 ↑ZAG, p62, muscle fiber atrophy 97
In vivo MAC16 mouse model ↑ZAG, weight loss, lipolysis 97
In vivo MAC16 and MAC13 mouse model ↑FDG uptake, succinate level, phosphocholine, weight loss,
MURF1, Serum LDL		 98
In vitro C26 conditioned C2C12
myoblasts		 ↑Ddit4/REDD1, Akt1, mTOR, LC3 II, p62
↓p-Akt1, p-mTOR, p-4E-BP1, p-p70S6K		 99
In vivo C26 xenograft model ↑Ddit4, Akt1, Akt2, PDPK1
↓p-Akt1, p-mTOR, p-4E-BP1, p-p70S6K		 99
In vitro C26 conditioned AML2 ↓mitochondrial membrane potential, H2O2 production, MFN2,
DRP1, FIS1, PINK		 34
In vivo HCT-116 mouse model ↑exosome density, miR-146b-5p, UCP1, PRDM6
↓leptin, ADIPSIN		 100
In vivo C26 mouse model ↑exosomes, miR-195a-5p, miR-125b-1-3p, muscle atrophy
↓Bcl-2		 101
Kidney cancer In vitro RXF393, SKRC39, A498, 786-O, SN12C ↓MyoD1, pan-MHC, mTOR, TGF-β 102
In vivo RXF393, SKRC39, A498, 786-O, SN12C mouse model ↓MyoD1, glycolytic signatures, body weight
↑lipolysis, p38 MAPK		 102
Lung cancer Ex vivo serum ↑TNF-α, ROS, GSH, vitamin E, IL-6 91
In vitro Exosomes from LLC ↑IL-6, atrogin-1, MURF1, myotube atrophy, ↓myotube diameters 91
In vivo LLC cells ↑gp130, STAT3, p-STAT3, atrogin-1, p38 103
In vitro PC-3, H1299 ↓cavin-3, p-ERK, EGFR1, glucose uptake, lactate production
↑p-Akt, HIF1α, pS6K, survivin		 104
In vivo Mouse fetus ↓cavin-3, p-ERK, PTEN, body weight
↑p-Akt, HIF1α, glycolysis, lipodystrophy		 104
In vitro LLC conditioned C2C12 myoblasts ↑REDD1,
↓ myotube diameter, muscle loss, p-Akt1, p-mTORC1		 105
In vitro Extracellular vesicles from LLC ↑lipolysis, p-HSL, UCP1, PTHrP 106
In vivo C57BL/6 ↑lipolysis, PTHR, PTHrP 106
In vivo LLC ↑IL-6, STAT3, atrophy
↓muscle weight, fat weight, BM-MNCs, NFATc1		 107
In vivo LLC ↑RAGE, S100B, HMGB1, IL-6, IL-3, IL-9, IL-12p40, IL-17A,
IFNγ, TNF-α, splenomegaly, muscle wasting
↓body weight, survival, IL-1α, MyoD, MyHC		 108
Ex vivo Patient serum, muscle biopsies ↑miR-424-5p, miR-424-3p, miR-450a-5p
↓miR-451a, miR-144-5p, muscle strength		 109
In vivo LLC ↑SAA, IL-6
↓PON1		 110
Pancreatic cancer In vitro MiaPaCa2, AsPC1,
BxPC3, HPAF-2, Panc-1,
C2C12		 ↑TNF-α, IL-1β, IFN-γ 111
In vivo MiaPaCa2 and AsPC1 xenograft ↑PCB, G-6-Pase, skeletal muscle proteolysis,
↓myosin, body weight, hepatic glycogen, ATGL, atrogin-1,
MURF1		 111
In vitro MiaPaCa2, AsPC1 ↑Cav-1, IGF1R, IR, glycolysis 112
In vivo MiaPaCa2 cells ↑ Cav-1, IGF1R, IR, skeletal muscle proteolysis, ↑lipolysis,
↓body weight		 112
Ex vivo Serum ↑GLP-1, apoC-II, apoC-III 113
Ex vivo Serum ↑ IL-6, glucocorticoids,
↓ ketone levels, food intake		 114
In vivo KPC ↑IL-6, glucocorticoids
↓ food intake, ketones, PPAR-α, ACADM, HMGCS2		 114
In vivo C57BL/6J ↑LCN2, E3 ubiquitin ligase, MAFBX, MURF1, FOXO1
↓ BNIP3, CTSL, GABARAPL, PPAR-γ, food intake		 115
Ex vivo Human tissue ↑ IL-6, cachexia 116
In vitro KPC 32908, C2C12, 3T3 ↑ IL-6, p-STAT3, E3 ubiquitin ligase, atrogin-1,
MAFBX, TRIM63/MURF1
↓ myotube diameter		 116
In vivo C57BL/6 ↑IL-6, muscle wasting
↓ survival		 116
In vitro C2C12 ↑atrogin-1, MURF1
↓MyHC		 117
In vivo C57BL/6 ↑macrophage mediated STAT3 activation
↓body weight, body strength, IL-6, TNF-α, IL-1α, IL-1β		 117
In vitro C2C12 ↑Sirt1, TRIM63, FBXO32, atrogin-1, NOX4
↓myotube width, total protein content, MyHC		 118
In vivo KPC mouse model
S2-013 orthotopic model		 ↑Sirt1, MURF1, atrogin-1, ZAG, UCP2,
↓body weight, forelimb grip strength, fat content, MyHC		 118
In vivo Pan02, FC1242 bearing mice ↑ZIP4, Zinc 119
Other In vivo Walker 256 cells ↓response to glucagon, isoproterenol, cAMP, phenylephrine,
↓liver ATP		 120
In vivo Walker 256 cells ↑leucine rich diet, ↓tumor FDG uptake, metastasis 121
In vitro C2C12 myoblasts ↑ atrogin-1, MURF1, E214k, FOXO1, USP2, UBC
↓ myoD, Pax3, p-Akt, MYH2, TNNC1, TPM3, TCAP,		 122
In vivo Myostatin cachexia
model		 ↓myoD, Pax3, ↑ atrogin-1, MURF1, E214k 122
In vivo CHO cells ↑TNF-20, weight loss, progressive death 13
Ex vivo Serum from cancer patients ↑ IL-15 123
In vivo MC38, LLC, CT26
bearing mice		 ↑PLA2G7 124

FATP1: fatty acid transport protein 1; CD36: cluster determinant 36; UCP1: uncoupling protein 1; p-p38: phospho p38; PPARγ: peroxisome proliferator-activated receptor gamma; p-PPARγ: phospho peroxisome proliferator-activated receptor gamma; UCP3: uncoupling protein 3; ERK: extracellular signal-regulated kinase; p-ERK: phospho extracellular signal-regulated kinase; P4HAI: prolyl 4-hydroxylase subunit alpha 1; PKM2: pyruvate kinase M2; ARHGDIB: rho GDP dissociation inhibitor beta; PGK1: phosphoglycerate kinase 1; LDHA: lactate dehydrogenase A; ALDA: aldolase, fructose bisphosphate A; GPD2: glycerol-3-phosphate dehydrogenase 2; ENO1: enolase 1; TPI1: triosephosphate isomerase 1; PGAM1: phosphoglycerol mutase 1; EEF1D: eukaryotic translation elongation factor 1 delta; PRDX1: peroxiredoxin 1; CAT: catalase; SPARC: secreted protein acidic and cysteine rich; COL1A1: collagen type 1 alpha 1 chain; COL1A2: collagen type 1 alpha 2 chain; Cav-1: caveolin 1; PYC: pyruvate carboxylase; G6PD: glucose-6-phosphate dehydrogenase; 4-HNE: 4-hydroxynonenal; ATP: adenosine triphosphate; SDS-MYL1: SDS-soluble myosin light chain 1; IL-6: interleukin-6; MURF1/TRIM63: muscle-specific RING finger protein 1/tripartite motif containing 63; LIF: leukemia inhibitory factor; STAT3: signal transducer and activator of transcription 3; p-STAT3: phospho signal transducer and activator of transcription; p-AMPK: phospho AMP-activated catalytic subunit; mTOR: mechanistic target of rapamycin kinase; p-mTOR: phospho mechanistic target of rapamycin kinase; Pax7: paired box 7; LC3bII/LC3BI: light chain 3 B 1/light chain 3 B 2; PBE: peroxisomal bifunctional enzyme; CPT1α: carnitine palmitoyltransferase 1 alpha; BAT: brown fat tissue; ZAG: zinc-alpha-2 glycoprotein; FDG: fluorodeoxyglucose; LDL: low-density lipoprotein; Ddit4/REDD1: DNA damage inducible transcript 4/regulated in development and DNA damage responses 1; Akt1: Akt serine/threonine kinase 1; p-Akt1: phospho Akt serine/threonine kinase 1; p-4E-BP1: phospho eukaryotic translation initiator factor 4E binding protein 1; p-p70S6K: P70 ribosomal S6 kinase; PDPK1: 3-phophoinositide dependent protein kinase 1; H2O2: hydrogen peroxide; MFN2: mitofusin 2; DRP1: dynamin-related protein 1; FIS1: fission mitochondrial 1; PINK: PTEN induced kinase; PRDM6: PR/SET domain 6; Bcl-2: B-cell CLL/lymphoma 2; TGF-β: transforming growth factor–beta; MHC: myocin heavy chain; MyoD1: myogenic differentiation 1; MAPK: mitogen activated protein kinase; TNF-α: tumor necrosis factor–alpha; ROS: reactive oxygen species; GSH: glutathione; gp130: glycoprotein 130; cavin-3: caveolae associated protein 3; EGFR1: epidermal growth factor receptor 1; HIF1-α: hypoxia inducible factor subunit alpha; pS6K: phospho S6 kinase; PTEN: phosphatase d tensin homolog; HSL: hormone sensitive lipase; p-HSL: phospho hormone sensitive lipase; PTHR: parathyroid hormone receptor; PTHrP: parathyroid hormone receptor–related protein; BM-MNCs: bone marrow–derived mononuclear cells; NFATc1: nuclear factor of activated T cells 1; RAGE: receptor for advanced glycation end product; S100B: S100 calcium binding protein B; HMGB1: high mobility group box 1; IL-3: interleukin-3; IL-9: interleukin-9; IL-12p40: interleukin-12 subunit p40; IL-17A: interleukin-17A; IFNγ: interferon gamma; IL-1α: interleukin-1 alpha; IL-1β: interleukin-1 beta; SAA: serum amyloid A1; PON1: paraoxonase 1; PCB: pyruvate carboxylase; G6pase: glucose 6 phosphatase; ATGL: adipose triglyceride lipase; IGF1R: insulin like growth factor 1 receptor; IR: insulin receptor; GLP1: glucagon like peptide 1; Apo CII: apolipoprotein C2; Apo CIII: apolipoprotein C3; PPAR-α: peroxisome proliferator-activated receptor alpha; ACADM: acyl CoA dehydrogenase medium chain; HMGCS2: 3-hydroxy-3-methylglutaryl-CoA synthase 2; LCN2: lipocalin 2; MAFBX/FBXO32: muscle atrophy F-box protein/F-box protein 32; FOXO1: Forkhead box O1; BNIP3: Bcl-2 interacting protein 3; CTSL: cathepsin L; GABARAPL: GABA type A receptor associated protein like; Sirt1: sirtuin 1, NOX4: NADPH oxidase 4; ZIP4: Zrt/Irt-like protein 4; cAMP: cyclic adenosine mono phosphate; E214K: ubiquitin conjugating enzyme E2 14 kDa; USP2: ubiquitin specific peptidase 2; UBC: ubiquitin C; Pax3: paired box 3; MYH2: myosin heavy chain 2; TNNC1: troponin C1; TPM3: tropomyosin 3; TCAP: titin-cap; TNF-20: tumor necrosis factor–20; IL-15: interleukin-15; PLA2G7: phospholipase A2 group 7.