A Novel 3-Dimensional Co-culture Method Reveals a Partial Mesenchymal to Epithelial Transition in Breast Cancer Cells Induced by Adipocytes

Pallegar, Nikitha K; Garland, Chantae; Mahendralingam, Mathepan; Viloria-Petit, Alicia; Christian, Sherri L.

doi:10.1007/s10911-018-9420-4

Cited by 24 publications

(32 citation statements)

References 38 publications

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“…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) Abbreviations: BC breast cancer; ER estrogen receptor; TNBC triple-negative BC; IL-6 interleukin 6; IL-8 interleukin 8; CCL2 chemokine ligand 2; CCL5 chemokine ligand 5; CAAs cancer-associated adipocytes; EMT epithelial-mesenchymal transition; IGFBP-2 insulin-like growth factor binding protein 2; G-CSF granulocyte colony-stimulating factor; DOX doxorubicin; PLOD2 lysyl hydroxylase 2; PAI-1 plasminogen activator inhibitor type 1 …”

Section: Discussionmentioning

confidence: 99%

“…ECM adaptation is essential for the progression and invasion of BC, which could be possibly altered by adipocytes. Interestingly, in an accessible 3-dimensional (3D) co-culture system, Pallegar et al demonstrated that adipocytes promoted a mesenchymal-to-epithelial transition (MET)-like change in mesenchymal TNBC cells, emphasizing the reciprocal interaction between high adiposity and BC metastasis with adipocyte abundance [81].…”

Section: Extracellular Matrix Remodelingmentioning

confidence: 99%

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Cancer-associated adipocytes: emerging supporters in breast cancer

Zhao

Zeng

et al. 2020

J Exp Clin Cancer Res

120

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Breast cancer (BC) is a malignant breast tumor confronted with high invasion, metastasis and recurrence rate, and adipocytes are the largest components in breast tissue. The aberrant adipocytes, especially the BC-neighbored cancer-associated adipocytes (CAAs), are found in the invasive front of BC. CAAs present a vicious phenotype compared with mature mammary adipocytes and mediate the crosstalk network between adipocytes and BC cells. By releasing multiple adipokines such as leptin, adiponectin, interleukin (IL)-6, chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5), CAAs play essential roles in favor of proliferation, angiogenesis, dissemination, invasion and metastasis of BC. This article reviews the recent existing CAAs studies on the functions and mechanisms of adipocytes in the development of BC, including adipokine regulating, metabolic reprogramming, extracellular matrix (ECM) remodeling, microRNAs (miRNAs) and immune cell adjusting. Besides, adipocyte secretome and cellular interactions are implicated in the intervention to BC therapy and autologous fat grafting of breast reconstruction. Therefore, the potential functions and mechanisms of CAAs are very important for unveiling BC oncogenesis and progress. Deciphering the complex network between CAAs and BC is critical for designing therapeutic strategies and achieving the maximum therapeutic effects of BC.

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Section: Discussionmentioning

confidence: 99%

Section: Extracellular Matrix Remodelingmentioning

confidence: 99%

Cancer-associated adipocytes: emerging supporters in breast cancer

Zhao

Zeng

et al. 2020

J Exp Clin Cancer Res

120

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“…Structures present in 5 images per replicate (minimum 10 structures per replicate) were traced manually, and the circularity measurement was obtained. A circularity value of >0.7 was classified as round/mass-like, 0.7-0.2 was classified as grape-like, and <0.2 was classified as stellate as reported previously [31]. Protein expression was analyzed using ImageJ by measuring the intensity of fluorescence of the whole image.…”

Section: Image Analysismentioning

confidence: 99%

Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture

Asante

Pallegar

Hoffmann

et al. 2020

IJMS

Self Cite

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Breast cancer is the second leading cause of cancer-related mortality among women globally with obesity being one risk factor. Obese breast cancer patients have at least a 30% increased risk of death from breast cancer compared to non-obese breast cancer patients because they present with larger tumors and generally have increased rates of metastasis. Moreover, obese breast cancer patients respond more poorly to treatment compared to non-obese patients, particularly pre-menopausal women diagnosed with triple negative breast cancer (TNBC). To help understand the molecular mechanisms underlying the increased metastasis associated with obesity, we previously established a three-dimensional culture system that permits the co-culture of adipocytes and TNBC cells in a manner that mimics an in vivo milieu. Using this system, we demonstrate that white adipose tissue from both lean and obese mice can induce a partial mesenchymal-to-epithelial transition (MET). Triple negative breast cancer cells adopt an epithelial morphology and have an increased expression of some epithelial markers, but they maintain the expression of mesenchymal markers, furnishing the breast cancer cells with hybrid properties that are associated with more aggressive tumors. Thus, these data suggest that adipose tissue has the potential to promote secondary tumor formation in lean and obese women. Further work is needed to determine if targeting the partial MET induced by adipose tissue could reduce metastasis.

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“…In 148 vitro treatment of whole tissue explants (De Vries et al, 2011, Magro et al, 2017 is an attractive 149 possibility, as they may convey key mechanistic information impossible to obtain by analysis of 150 biopsies. Another alternative is the use of three-dimensional co-culture models that incorporate 151 ECM and stromal cells of interest in addition to the epithelial cells, as those recently developed 152 by our group (Pallegar et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Peer Review #3 of "TGF-beta signalling in bovine mammary gland involution and a comparative assessment of MAC-T and BME-UV1 cells as in vitro models for its study (v0.2)"

2019

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The goal of the dairy industry is ultimately to increase lactation persistency, which is the length of time during which peak milk yield is sustained. Lactation persistency is determined by the balance of cell apoptosis and cell proliferation; when the balance is skewed toward the latter, this results in greater persistency. Thus, we can potentially increase milk production in dairy cows through manipulating apoptogenic and antiproliferative cellular signalling that occurs in the bovine mammary gland. Transforming growth factor beta 1 (TGFβ1) is an antiproliferative and apoptogenic cytokine that is upregulated during bovine mammary gland involution. Here we discuss possible applications of TGFβ1 signalling for the purposes of increasing lactation persistency. We also compare the features of MAC-T and BME-UV1 cells, two popular bovine mammary epithelial cell lines, to assess their appropriateness for the study of TGFβ1 signalling.TGFβ1 induces apoptosis and arrests cell growth in BME-UV1 cells, and this was reported to involve suppression of the somatotropic axis. Conversely, there is no proof that exogenous TGFβ1 induces apoptosis of MAC-T cells.In addition to TGFβ1's different effects on apoptosis,hormones and growth factors have distinct effects on TGFβ1 secretion and synthesis in MAC-T and BME-UV1 cell lines. MAC-T and BME-UV1 cells may behave differently in response to TGFβ1 due to their contrasting phenotypes; MAC-T cells have a profile indicative of both myoepithelial and luminal populations, while the BME-UV1 cells exclusively contain a luminal-like profile. Depending on the nature of the research question, the use of these cell lines as models to study TGFβ1 signalling should be carefully tailored to the questions asked. ABSTRACT 11The goal of the dairy industry is ultimately to increase lactation persistency, which is the 12 length of time during which peak milk yield is sustained. Lactation persistency is determined by 13 the balance of cell apoptosis and cell proliferation; when the balance is skewed toward the latter, 14 this results in greater persistency. Thus, we can potentially increase milk production in dairy 15 cows through manipulating apoptogenic and antiproliferative cellular signalling that occurs in 16 the bovine mammary gland. Transforming growth factor beta 1 (TGFβ1) is an antiproliferative 17 and apoptogenic cytokine that is upregulated during bovine mammary gland involution. Here we 18 discuss possible applications of TGFβ1 signalling for the purposes of increasing lactation 19 persistency. We also compare the features of MAC-T and BME-UV1 cells, two popular bovine 20 mammary epithelial cell lines, to assess their appropriateness for the study of TGFβ1 signalling. 21 TGFβ1 induces apoptosis and arrests cell growth in BME-UV1 cells, and this was reported to 22 involve suppression of the somatotropic axis. Conversely, there is no proof that exogenous 23 TGFβ1 induces apoptosis of MAC-T cells. In addition to TGFβ1's different effects on apoptosis, 24 hormones and growth factors have disti...

show abstract

A Novel 3-Dimensional Co-culture Method Reveals a Partial Mesenchymal to Epithelial Transition in Breast Cancer Cells Induced by Adipocytes

Cited by 24 publications

References 38 publications

Cancer-associated adipocytes: emerging supporters in breast cancer

Cancer-associated adipocytes: emerging supporters in breast cancer

Adipose Tissue from Lean and Obese Mice Induces a Mesenchymal to Epithelial Transition-Like Effect in Triple Negative Breast Cancers Cells Grown in 3-Dimensional Culture

Peer Review #3 of "TGF-beta signalling in bovine mammary gland involution and a comparative assessment of MAC-T and BME-UV1 cells as in vitro models for its study (v0.2)"

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