From: Cancer-associated adipocytes: emerging supporters in breast cancer
Breast cancer subtype | Model | Impact of CAAs on breast cancer subtypes | Ref. |
---|---|---|---|
ER-positive | Co-culture model (MCF-7) | A direct co-culture between murine 3T3-L1-derived adipocytes and BC cells of various molecular subtypes induced an EMT phenotype and enhanced their proliferation, migration, and invasion capabilities. | [11] |
ER-negative | Co-culture model (MDA- MB-231, MDA-MB-468) | ||
ER-positive | Co-culture model (MCF-7) | CAA-conditioned medium increased the cell migration of both MCF-7 and MDA-MB-231 cells via IL-6 and CCL2. | [12] |
ER-negative | Co-culture model (MDA-MB-231) | ||
ER-positive | Co-culture model (ZR 75.1) | Mature adipocytes were able to stimulate the invasive capacities of murine and human BC cell lines that are either positive (ZR 75.1) or negative (SUM159PT, 67NR, 4 T1) for the ER. Coculture with adipocytes had no effect on ZR 75.1, 67NR or 4T1 proliferation in contrast to SUM159PT cells. | [14] |
ER-negative | Co-culture model (SUM 159PT, 67NR, 4T1) | ||
Luminal A | Co-culture model (MCF-7); human invasive ductal carcinoma sample | A total of 1126 and 1218 proteins were identified in MCF-7 and MDA-MB-231 cells, respectively. Among these, 85 (MCF-7) and 63 (MDA-MB- 231) had an average fold change > 1.5 following co-culture. | [16] |
TNBC | Co-culture model (MDA-MB-231); human invasive ductal carcinoma sample | ||
TNBC | Co-culture model (MDA-MB-231, MDA-MB-468); clinical samples in the dataset | Adipocytes could facilitate the pro-metastasis role in TNBC and non-TNBC via PLOD2-dependent way. PLOD2 expression was much higher in TNBC patients, compared to non-TNBC patients. | [24] |
non-TNBC | Co-culture model (SK-BR-3); clinical samples in the dataset | ||
ER-positive | Co-culture model (MCF-7, ZR-75-1) | The transition of adipocytes into more inflammatory CAAs resulted in proliferation-promoting effect in ER-positive BC cells such as MCF7 and ZR-75-1 but not in ER-negative cells; aromatase levels were upregulated in CAAs that might favor the growth of ER-positive BC cells. | [41] |
ER-negative | Co-culture model (MDA-MB-231, Hs578T) | ||
Not-given | Human BC samples | The expression of IL-6 was up-regulated in CAAs in human BC tissues. | |
ER-positive | Co-culture model (MCF-7, T47D) | In ER-positive cell lines, top upregulated genes showed significant enrichment for hormone receptor target genes. In triple-negative MDA-MB-231 cells, co-culture with adipocytes led to the induction of pro-inflammatory genes, mainly involving genes of the Nf-κB signaling pathway, and increased secretion of the pro-inflammatory interleukins IL-6 and IL-8. | [42] |
TNBC | Co-culture model (MDA-MB-231) | ||
Luminal A | Co-culture model (MCF-7) | Human adipocytes could enhance proliferation, migration and invasion abilities of MDA-MB-468 and MCF-7 cells after co-culture, and these effects were more profound in MDA-MB-468 cells compared with MCF-7, which are non-invasive cells. | [43] |
TNBC | Co-culture mode (MDA-MB-468) | ||
TNBC | Co-culture model (MDA-MB-231, MDA-MB-453) | Elevated secretion of CCL5 in adipocytes co-cultured with the TNBC cell lines heightened the EMT effect, thereby promoting tumor growth and lung and liver metastasis. | [51] |
TNBC | Co-culture model (E0771); in vivo mouse orthotopic tumor model | Conditioned media from adipocytes supported E0771 cell proliferation and enhanced cell migration in vitro; adipocytes not only accelerated breast tumor growth, but also enhanced vascularization in vivo. | [54] |
ER-positive | Co-culture model (MCF-7) | The co-culture media of human MCF-7 BC cells and human mature adipocytes increased the motility of MCF-7 cells through IGFBP-2. | [55] |
Not-given | 10 metastatic pathologic samples and 10 non-metastatic pathologic samples | Metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue, whereas adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did adipocytes surrounding non-metastatic breast tumors. | |
ER-positive | In vivo zebrafish model (MCF-7, T47D) | Breast adipocyte increased the dissemination of ER-positive BC cells in the zebrafish model of metastasis, while dissemination of the more aggressive and metastatic BC cells such as ER-negative was unaffected. | [57] |
ER-negative | In vivo zebrafish model (MDA-MB-231) | ||
Not-given | Human invasive ductal carcinoma sample | CAAs isolated from 10 invasive breast carcinomas were pro-inflammatory and exhibited active phenotypes, including higher proliferative, invasive and migratory capacities. | [58] |
TNBC | Co-culture model (MDA-MB-231, BT549) | CAAs could enhance migration and invasion of TNBC cells, while the effect of CAAs on ER-positive BC cells were limited. | [59] |
ER-positive | Co-culture model (MCF-7, T47D) | ||
Not-given | Human BC tissue sample | Elevated G-CSF expression in adipocytes was well correlated with activated Stat3 signal in cancer cells. | |
ER-negative | Co-culture model (M28N2, M27H4, M6) | Mammary adipose tissue-derived lysophospholipids promoted ER-negative mammary epithelial cell proliferation. | [63] |
Luminal A | Co-culture model (MCF-7) | Proliferation, migration and invasion were increased in BC cells, which was most prominent for the highly invasive SUM159 cells and, to a lesser extent, for the less invasive MCF7 cells. | [78] |
TNBC | Co-culture model (SUM159) | ||
Not-given | Human invasive breast carcinoma sample | Collagen reorganization at the tumor-adipose periphery, as well as the positive relevance between PAI-1 and PLOD2 were found in invasive breast carcinoma, revealing a new stromal collagen network that favors tumor invasion and metastasis establish between BC cells and surrounding adipocytes at the tumor invasive front. | [80] |
TNBC | Co-culture model (MDA-MB-231, Hs578t) | Adipocytes and adipocyte-derived conditioned media, but not pre-adipocytes, caused the mesenchymal MDA-MB-231 and Hs578t cells to form significantly more epithelial-like structures when compared to the typical stellate colonies formed in control 3D cultures. MCF7 cells had a less dramatic shift as they normally have a more epithelial-like structure in 3D culture. | [81] |
Luminal A | Co-culture model (MCF7) | ||
ER-positive | Co-culture model (T47D) | Adipocytes caused DOX resistance in all the cell lines studied, independently of the BC subtypes. | [104] |
HER2-positive | Co-culture model (MDA-MB453, BT-474) | ||
TNBC | Co-culture model (MDA-MB436, MDA-MB231, M-Wnt, E0771) |