Molecular insights into the interplay between adiposity, breast cancer and bone metastasis

Soni, Sneha; Torvund, Meaghan; Mandal, Chandi C.

doi:10.1007/s10585-021-10076-0

Cited by 10 publications

(6 citation statements)

References 202 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In breast cancer cells, the most important pathways for this process are STAT, Hedgehog, protein kinase C (PKC), MAPK, Notch, and Hippo, with hundreds of downstream genes responsible for enhanced stemness [ 201 ]. Obesity increases systemic levels as well as cellular secretion of many cytokines and adipokines including leptin, IL6, TNFα, IGF1, fatty acid binding protein 4 (FABP4), and resistin, which are all involved in regulating the pathways associated with the development of CSCs in breast cancer tissue [ 202 ]. In accordance with this, Sabol et al showed that patient-derived xenograft (PDX) tumors co-cultured with obese ASCs increased the formation of metastases and the number of CD44 + CD24 − breast cancer stem cells in a severely immunodeficient (SCID) mouse model [ 124 ].…”

Section: Mutual Interaction Between Ascs/mscs and Breast Cancer Cellsmentioning

confidence: 99%

Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer

Ritter

Kreis

Hoock

et al. 2022

Cancers

View full text Add to dashboard Cite

Breast cancer is the most frequently diagnosed cancer and a common cause of cancer-related death in women. It is well recognized that obesity is associated with an enhanced risk of more aggressive breast cancer as well as reduced patient survival. Adipose tissue is the major microenvironment of breast cancer. Obesity changes the composition, structure, and function of adipose tissue, which is associated with inflammation and metabolic dysfunction. Interestingly, adipose tissue is rich in ASCs/MSCs, and obesity alters the properties and functions of these cells. As a key component of the mammary stroma, ASCs play essential roles in the breast cancer microenvironment. The crosstalk between ASCs and breast cancer cells is multilateral and can occur both directly through cell–cell contact and indirectly via the secretome released by ASC/MSC, which is considered to be the main effector of their supportive, angiogenic, and immunomodulatory functions. In this narrative review, we aim to address the impact of obesity on ASCs/MSCs, summarize the current knowledge regarding the potential pathological roles of ASCs/MSCs in the development of breast cancer, discuss related molecular mechanisms, underline the possible clinical significance, and highlight related research perspectives. In particular, we underscore the roles of ASCs/MSCs in breast cancer cell progression, including proliferation and survival, angiogenesis, migration and invasion, the epithelial–mesenchymal transition, cancer stem cell development, immune evasion, therapy resistance, and the potential impact of breast cancer cells on ASCS/MSCs by educating them to become cancer-associated fibroblasts. We conclude that ASCs/MSCs, especially obese ASCs/MSCs, may be key players in the breast cancer microenvironment. Targeting these cells may provide a new path of effective breast cancer treatment.

show abstract

Section: Mutual Interaction Between Ascs/mscs and Breast Cancer Cellsmentioning

confidence: 99%

Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer

Ritter

Kreis

Hoock

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…Adiponectin and resistin belong to the adipokine family and are secreted by mature adipocytes. FABP4 and LIPE (hormone-sensitive lipase) are markers of adipocyte differentiation [ 19 ], just like PPARγ (peroxisome proliferator-activated receptor γ), a key regulator of adipogenesis and adipocyte differentiation, whereas perilipin protects lipid droplets from lipolysis [ 20 ]. Real-time PCR analysis showed that expression levels of LIPE , resistin , perilipin , FABP4 , adiponectin, and PPARγ were significantly reduced in adipocytes co-cultured with all CRC cells used in comparison to the control consisting of mono-cultured adipocytes (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mutual impact of adipocytes and colorectal cancer cells growing in co-culture conditions

Olszańska

Pietraszek-Gremplewicz

Domagalski

et al. 2023

Cell Commun Signal

View full text Add to dashboard Cite

Background Colorectal cancer (CRC) is the third most common malignancy worldwide. CRC cells are situated in an adipocyte-rich microenvironment, which leads to interactions between adipocytes and CRC cells. Upon exposure to cancer cells, adipocytes transform into cancer-associated adipocytes (CAAs), and as a result, they gain features that promote tumor progression. The aim of this research was to shed more light on the detailed role of interactions between adipocytes and CRC cells associated with cancer progression in the context of these alterations. Methods To implement adipocyte-CRC cell interaction, a co-culture model was applied. The analyses mainly focused on the metabolic modifications within CAAs and CRC cells, as well as the proliferation and migration potential of CRC cells. The impact of CRC on adipocytes was investigated by qRT-PCR analysis and Oil Red O staining. Proliferation and migration of CRC cells upon co-culture were tested with videomicroscopy, XTT, and a wound healing assay. Metabolic changes within CAAs and CRC cells were investigated based on lipid droplet formation, cell cycle analysis, gene and protein expression by qRT-PCR, and western blotting techniques. Results CRC cells induced reprogramming of adipocytes into CAAs, which was connected with downregulation of lipid droplet formation in CAAs and alteration in adipocyte features. CAAs showed decreased metabolism-related gene expression, phosphorylation of Akt, ERK kinases, STAT3, and lactate secretion in comparison to the control. CAAs also promoted the migration, proliferation, and lipid droplet accumulation of CRC cells. After co-culturing with adipocytes, there was a shift to the G2/M phase of the cell cycle according to the differences in cyclin expression. Conclusion There are complex bidirectional interactions between adipocytes and CRC cells that may be connected with the induction of CRC cell progression.

show abstract

“…In obesity, mature adipocytes increase the secretion of cytokines compared to mature adipocytes in normal adipose tissue [ 135 ]. Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) not only play a potential role in the initiation of breast cancer ( Section 3.2.1 ), but also in the progression of breast cancer [ 135 , 136 , 137 , 138 ]. The proposed mechanisms are outlined below.…”

Section: Breast Cancer Progression and Local Obesity-associated Biomarkersmentioning

confidence: 99%

Local Biomarkers Involved in the Interplay between Obesity and Breast Cancer

Holm

Rosendahl

Borgquist

2021

Cancers

View full text Add to dashboard Cite

Obesity is associated with an increased risk of breast cancer, which is the most common cancer in women worldwide (excluding non-melanoma skin cancer). Furthermore, breast cancer patients with obesity have an impaired prognosis. Adipose tissue is abundant in the breast. Therefore, breast cancer develops in an adipose-rich environment. During obesity, changes in the local environment in the breast occur which are associated with breast cancer. A shift towards a pro-inflammatory state is seen, resulting in altered levels of cytokines and immune cells. Levels of adipokines, such as leptin, adiponectin, and resistin, are changed. Aromatase activity rises, resulting in higher levels of potent estrogen in the breast. Lastly, remodeling of the extracellular matrix takes place. In this review, we address the current knowledge on the changes in the breast adipose tissue in obesity associated with breast cancer initiation and progression. We aim to identify obesity-associated biomarkers in the breast involved in the interplay between obesity and breast cancer. Hereby, we can improve identification of women with obesity with an increased risk of breast cancer and an impaired prognosis. Studies investigating mammary adipocytes and breast adipose tissue in women with obesity versus women without obesity are, however, sparse and further research is needed.

show abstract

Molecular insights into the interplay between adiposity, breast cancer and bone metastasis

Cited by 10 publications

References 202 publications

Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer

Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer

Mutual impact of adipocytes and colorectal cancer cells growing in co-culture conditions

Local Biomarkers Involved in the Interplay between Obesity and Breast Cancer

Contact Info

Product

Resources

About