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

Ritter, Andreas; Kreis, Nina-Naomi; Hoock, Samira Catharina; Solbach, Christine; Louwen, Frank; Yuan, Juping

doi:10.3390/cancers14163908

Cited by 28 publications

(17 citation statements)

References 269 publications

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“…6 D-F, 2 nd , 3 rd and 5 th rows). This is in accordance with multiple reports highlighting a general tumor-promoting effect of MSCs co-cultured with BC cell lines [ 57 ]. The common pattern of breast cancer cells co-cultured with ln-aT, ln-dT or ob-dT bASCs indicated a changed expression of important cytoskeleton genes RAC2 and VIM , ECM genes LAMC2 and ICAM1 , DNA repair genes ATM and BIRC2–3, and cell cycle regulating genes CCNA1 , CCND2 and CENPE (Fig.…”

Section: Resultssupporting

confidence: 93%

“…Despite intense research, questions remain regarding the relationship and interaction between MSCs/ASCs and malignant cells. There are various reports suggesting tumor-promoting effects on the one hand and tumor-inhibiting functions on the other hand [ 53 , 57 , 64 ]. In the present work, we show close reciprocal exchange between bASCs of the TME and breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Cancer-educated mammary adipose tissue-derived stromal/stem cells in obesity and breast cancer: spatial regulation and function

Ritter

Kreis

Roth

et al. 2023

J Exp Clin Cancer Res

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Background 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. Breast adipose tissue-derived mesenchymal stromal/stem cells (bASCs) are crucial components of the tumor microenvironment. A key step initially involved in this process might be the de-differentiation of bASCs into tumor supporting phenotypes. Methods In the present work, we isolated bASCs from adipose tissues adjacent to the tumor (aT bASCs) from lean- (ln-aT bASCs, BMI ≤ 25) and breast cancer patients with obesity (ob-aT bASCs, BMI ≥ 35), and analyzed their phenotypes with functional assays and RNA sequencing, compared to their counterparts isolated from adipose tissues distant from the tumor (dT bASCs). Results We show that ln-aT bASCs are susceptible to be transformed into an inflammatory cancer-associated phenotype, whereas ob-aT bASCs are prone to be cancer-educated into a myofibroblastic phenotype. Both ln-aT- and ob-aT bASCs compromise their physiological differentiation capacity, and upregulate metastasis-promoting factors. While ln-aT bASCs stimulate proliferation, motility and chemoresistance by inducing epithelial-mesenchymal transition of low malignant breast cancer cells, ob-aT bASCs trigger more efficiently a cancer stem cell phenotype in highly malignant breast cancer cells. Conclusion Breast cancer-associated bASCs are able to foster malignancy of breast cancer cells by multiple mechanisms, especially, induction of epithelial-mesenchymal transition and activation of stemness-associated genes in breast cancer cells. Blocking the de-differentiation of bASCs in the tumor microenvironment could be a novel strategy to develop an effective intervention for breast cancer patients. Significance This study provides mechanistic insights into how obesity affects the phenotype of bASCs in the TME. Moreover, it highlights the molecular changes inside breast cancer cells upon cell-cell interaction with cancer-educated bASCs. Graphical abstract

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Section: Resultssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Cancer-educated mammary adipose tissue-derived stromal/stem cells in obesity and breast cancer: spatial regulation and function

Ritter

Kreis

Roth

et al. 2023

J Exp Clin Cancer Res

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“…Hyperplasia may account for this increase as well as homing, which preponderantly depends on the SDF-1/CXCR4 axis with increased expression of CXCR4 in cancer cells and SDF-1 secretion by ASCs. IL-8 and CXCL-1, whose secretions are increased in obese ASCs, have also been shown to contribute to the recruitment of ASCs into the tumor site [127][128][129][130].…”

Section: Role Of Obese Ascs In Increased Vascularization and Tumor Gr...mentioning

confidence: 99%

Pathogenic Role of Adipose Tissue-Derived Mesenchymal Stem Cells in Obesity and Obesity-Related Inflammatory Diseases

Pestel

Blangero

Eljaafari

2023

Cells

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Adipose tissue-derived mesenchymal stem cells (ASCs) are adult stem cells, endowed with self-renewal, multipotent capacities, and immunomodulatory properties, as mesenchymal stem cells (MSCs) from other origins. However, in a pathological context, ASCs like MSCs can exhibit pro-inflammatory properties and attract inflammatory immune cells at their neighborhood. Subsequently, this creates an inflammatory microenvironment leading to ASCs’ or MSCs’ dysfunctions. One such example is given by obesity where adipogenesis is impaired and insulin resistance is initiated. These opposite properties have led to the classification of MSCs into two categories defined as pro-inflammatory ASC1 or anti-inflammatory ASC2, in which plasticity depends on the micro-environmental stimuli. The aim of this review is to (i) highlight the pathogenic role of ASCs during obesity and obesity-related inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease, and cancer; and (ii) describe some of the mechanisms leading to ASCs dysfunctions. Thus, the role of soluble factors, adhesion molecules; TLRs, Th17, and Th22 cells; γδ T cells; and immune checkpoint overexpression will be addressed.

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“…Another cellular element that makes up breast cancer TME is adipocytes. Recent findings suggest that they promote the advancement of the tumor through a reciprocal and constantly evolving interaction with the cancerous cells and TME [69,70]. For example, breast cancer cells secrete pro-inflammatory cytokines such as IL-6 and tumor necrosis factor (TNF-α) that can promote adipose tissue inflammation and disrupt normal adipose tissue function [71].…”

Section: Breast Cancer Cell Secretome and Stromal Componentsmentioning

confidence: 99%

Impact of the Cancer Cell Secretome in Driving Breast Cancer Progression

Zahari

Syafruddin

Mohtar

2023

Cancers

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Breast cancer is a complex and heterogeneous disease resulting from the accumulation of genetic and epigenetic alterations in breast epithelial cells. Despite remarkable progress in diagnosis and treatment, breast cancer continues to be the most prevalent cancer affecting women worldwide. Recent research has uncovered a compelling link between breast cancer onset and the extracellular environment enveloping tumor cells. The complex network of proteins secreted by cancer cells and other cellular components within the tumor microenvironment has emerged as a critical player in driving the disease’s metastatic properties. Specifically, the proteins released by the tumor cells termed the secretome, can significantly influence the progression and metastasis of breast cancer. The breast cancer cell secretome promotes tumorigenesis through its ability to modulate growth-associated signaling pathways, reshaping the tumor microenvironment, supporting pre-metastatic niche formation, and facilitating immunosurveillance evasion. Additionally, the secretome has been shown to play a crucial role in drug resistance development, making it an attractive target for cancer therapy. Understanding the intricate role of the cancer cell secretome in breast cancer progression will provide new insights into the underlying mechanisms of this disease and aid in the development of more innovative therapeutic interventions. Hence, this review provides a nuanced analysis of the impact of the cancer cell secretome on breast cancer progression, elucidates the complex reciprocal interaction with the components of the tumor microenvironment and highlights emerging therapeutic opportunities for targeting the constituents of the secretome.

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

Cited by 28 publications

References 269 publications

Cancer-educated mammary adipose tissue-derived stromal/stem cells in obesity and breast cancer: spatial regulation and function

Cancer-educated mammary adipose tissue-derived stromal/stem cells in obesity and breast cancer: spatial regulation and function

Pathogenic Role of Adipose Tissue-Derived Mesenchymal Stem Cells in Obesity and Obesity-Related Inflammatory Diseases

Impact of the Cancer Cell Secretome in Driving Breast Cancer Progression

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