Adipocytes in Breast Cancer, the Thick and the Thin
Abstract
1. Introduction
2. Adipogenesis and the Adipose Organ
2.1. The Adipogenesis Process
2.2. The Adipose Tissue
2.3. Mammary Adipocytes
3. Epidemiological/Clinical Association between Obesity and BC
4. Evidence of the Pro-Tumorigenic Effect of the Adipocyte-Tumor Cell Crosstalk
5. Mechanisms Behind the Pro-Tumorigenic Effect of Adipocytes
5.1. Inflammation
IL-6 and TNF-α
5.2. Estrogens
5.3. Adipokines
5.3.1. Adiponectin and Leptin
5.3.2. Autotaxin and Resistin
5.3.3. HGF and IGF
5.4. Extracellular Matrix Remodeling
5.5. Metabolic Shift
6. Adipocytes in Cancer-Associated Cachexia
7. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristic | Obesity | CAAs | Cachexia | |
---|---|---|---|---|
In Vivo | In Vitro | |||
Size/TG stores | ↑ A size [23] | ↓ A size [19] and lipid droplet size [24] | ↓ lipid droplets size and number [19,24] | ↓ A size and TG content [25] |
Adipogenesis regulators | ↓ C/EBPα and PPARγ [26] | - | ↓ PPARγ and C/EBPα [19,24] | ↓ PPARγ and C/EBPα [25,27] |
UCP1 (browning) | ↑ in brown AT [28] ↓ in white AT [29] | ↑ [30] | - | ↑ [31] |
Glucose transport | ↓ GLUT4 [28] | - | ↓ GLUT4 and IRS1 [24] | ↓ GLUT4 [32] |
Lipogenesis | ↑ in white AT [33] | ↓ (↓HOXC8, HOXC9, FABP4, and HSL) [30] | ↓ (↓ FABP4, HSL, ATGL, CIDEA, and FASN) [24] | ↓ (↓ SREBP-1c) [32] |
Lipolytic activity (ATGL/HSL) | ↑ in subc. A [34] | ↓ HSL [30] | ↓ HSL [19] | ↑ HSL [35] |
Feature | Effect | Adipocyte Comments | Ref |
---|---|---|---|
Proliferation | ↑ in ER+ (MCF-7, ZR75-1, T47-D) cells by mature A = in ER+ cells by preadipocytes = in ER- (MMT 060562) cells by mature A | Primary mature subcutaneous rat A and preadipocytes 7 days of direct contact in 3D collagen gel | [61] |
↑ in SUM159PT by mature A = in ZR 75.1, 67NR, 4T1 by mature A | 3T3-F442A cell line 3 days coculture in transwell | [19] | |
↑ in BC cell lines (MCF7, MDA-MB-231, N-453, N-435S, -468) by mature A | Mature 3T3-L1 2 days coculture in transwell | [60] | |
Tumor growth | EO771 cells injected in brown AT > white AT > subcutaneous AT | Dorsal subcutaneous fat, inguinal white AT, interscapular brown AT of C57BL/6 mice | [62] |
↑ SKOV3ip1 ovarian cancer cells injected with A vs. tumor cells alone | Human primary omental A Nude mice | [21] | |
EMT/ stemness | ↑ E-CAD expression in T47D and MCF-7 cells by preadipocytes = E-CAD in ZR75-1 and MMT 060562 cells by preadipocytes = E-CAD expression in T47D, MCF-7, ZR75-1 and MMT 060562 cells by mature A | Primary mature subcutaneous rat A and preadipocytes 7 days of direct contact in 3D collagen gel | [61] |
↑ change in morphology in MCF-7, MDA-MB-435S, -231 cells by mature A = in MDA-MB-453, -468 cells ↓ E-CAD in MCF7 cells by mature A ↑ Vim in MCF-7, MDA-MB-231 and-435S cells by mature A | 3T3-L1 A 2 days coculture in transwell | [60] | |
Migration/ Invasion | ↑ invasion of ZR 75.1, 67NR, SUM159PT, 4T1 cells by mature A ↑ in BC cell lines by CM from CAAs = in BC cell lines by CM from “naive” A ↑ number of metastases in BALB/c mice injected with 4T1 cells previously cultivated with A | 3T3-F442A cell line Indirect coculture/CM | [19] |
↑ MCF7, MDA-MB-231, -468, -453, -435S) by mature A ↑ TN (MDA-MB-231, -468, -435S) > ER+ MCF7, HER2+ MDA-MB-453 | 3T3-L1 A 2 days coculture in transwell | [60] | |
Metabolic reprogramming | ↑ accumulation of lipids in T47D and MDA-MB-231 in coculture with A | Human primary omental A | [21] |
Molecules | Obesity | CAAs | Cachexia | |
---|---|---|---|---|
In Vivo | In Vitro | |||
TNF-α | ↑ [64] | ↑ [30] | ↑ [19] | ↑ [65,66] |
IL-6 | ↑ [67,68] | ↑ [19] | ↑ [19] | ↑ [65,66] |
IL-1β | ↑ [69] | - | ↑ [19] | ↑ [66] |
CCL2 | ↑ [70] | - | ↑ [71] | ↑ [66,72] |
CCL5 | ↑ [73] | ↑ [74] | - | - |
Aromatase | ↑ [75] | ↑ [76] | - | - |
Leptin | ↑ [77,78] | ↑ [30] | ↓ [24] | ↓ [79] * |
Adiponectin | ↓ [80] * | ↓ [19,30] | ↓ [19,24] | ↑ [81] * |
Resistin | ↑ [67] * | ↑ [20] | ↓ [19,24] | - |
Autotaxin | ↑ [82,83,84] | ↑ [85] | - | - |
HGF | ↑ [86] | ↑ [20] | - | - |
IGF-1 | ↑ [87,88] | - | - | - |
PAI-1 | ↑ [89,90] | ↑ [20] | ↑ [19] | - |
COL6A3 | ↑ [91] | ↑ [20] | - | - |
MMP11 | - | ↑ [20] | ↑ [19,24] | - |
MMPs | ↑ [92] | ↑ [20] | ↑ (MMP9, [24]) | ↑ (MMP2 and MMP9, [93]) |
Collagen | ↑ (fibrosis, [94]) | - | ↑ (COL I, [37]) | ↑ (COL I, III, VI, [27,65]) |
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Rybinska, I.; Agresti, R.; Trapani, A.; Tagliabue, E.; Triulzi, T. Adipocytes in Breast Cancer, the Thick and the Thin. Cells 2020, 9, 560. https://doi.org/10.3390/cells9030560
Rybinska I, Agresti R, Trapani A, Tagliabue E, Triulzi T. Adipocytes in Breast Cancer, the Thick and the Thin. Cells. 2020; 9(3):560. https://doi.org/10.3390/cells9030560
Chicago/Turabian StyleRybinska, Ilona, Roberto Agresti, Anna Trapani, Elda Tagliabue, and Tiziana Triulzi. 2020. "Adipocytes in Breast Cancer, the Thick and the Thin" Cells 9, no. 3: 560. https://doi.org/10.3390/cells9030560
APA StyleRybinska, I., Agresti, R., Trapani, A., Tagliabue, E., & Triulzi, T. (2020). Adipocytes in Breast Cancer, the Thick and the Thin. Cells, 9(3), 560. https://doi.org/10.3390/cells9030560