The Primary Cilium of Adipose Progenitors Is Necessary for Their Differentiation into Cancer-Associated Fibroblasts that Promote Migration of Breast Cancer Cells In Vitro

Peraldi, Pascal; Ladoux, Annie; Giorgetti‐Peraldi, Sophie; Dani, Christian

doi:10.3390/cells9102251

Cited by 5 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This comparison revealed that cilium size was not similar in separate APCs derived from breast tissue of the same patient. Consistent with our previous data highlighting the importance of primary cilium elongation for adipose differentiation [ 26 , 38 ], we can also hypothesize that primary cilium size represents a key determinant in driving cell fate. Population 1 preferentially expressed INHBA and CD142 , two markers that are associated with low adipogenic potential.…”

Section: Discussionsupporting

confidence: 92%

“…The expression of αSMA was preferentially induced in Population 1, indicating that this population was more prone to acquire a myofibroblastic phenotype. We used the “semi” coculture method of APCs and cancer cells that we developed [ 26 ] to evaluate the impact of MCF7 and T47D to trigger the secretome of both cell types to induce the CAF phenotype. This technique allows for the analysis of APC proteins without any interference with cancer cell proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Based on the markers they express, they can be classified as myofibroblast (Myo) CAFs, inflammatory CAFs, vascular CAFs, cyclic CAFs, or developmental CAFs [ 24 , 25 ], although no clear consensus has been adopted for an explicit classification so far. The differentiation of APCs into MyoCAFs has been reported to be dependent on the presence of a primary cilium and induced by TGFβ [ 26 ]. MyoCAFs express α-smooth muscle actin (αSMA).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of Human Breast Adipose Tissue Progenitors Displaying Distinct Differentiation Potentials and Interactions with Cancer Cells

et al. 2022

Self Cite

View full text Add to dashboard Cite

Breast adipose tissue (AT) participates in the physiological evolution and remodeling of the mammary gland due to its high plasticity. It is also a favorable microenvironment for breast cancer progression. However, information on the properties of human breast adipose progenitor cells (APCs) involved in breast physiology or pathology is scant. We performed differential enzymatic dissociation of human breast AT lobules. We isolated and characterized two populations of APCs. Here we report that these distinct breast APC populations selectively expressed markers suitable for characterization. The population preferentially expressing ALPL (MSCA1) showed higher adipogenic potential. The population expressing higher levels of INHBA and CD142 acquired myofibroblast characteristics upon TGF-β treatment and a myo-cancer-associated fibroblast profile in the presence of breast cancer cells. This population expressed the immune checkpoint CD274 (PD-L1) and facilitated the expansion of breast cancer mammospheres compared with the adipogenic population. Indeed, the breast, as with other fat depots, contains distinct types of APCs with differences in their ability to specialize. This indicates that they were differentially involved in breast remodeling. Their interactions with breast cancer cells revealed differences in the potential for tumor dissemination and estrogen receptor expression, and these differences might be relevant to improve therapies targeting the tumor microenvironment.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Human Breast Adipose Tissue Progenitors Displaying Distinct Differentiation Potentials and Interactions with Cancer Cells

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Other molecular mechanisms proposed for CAF activation include Notch/Eph-ephrin signaling, ECM composition in the TME, DNA damage, physiological stress, inflammatory stimuli, RTK ligands, and TGFβ-mediated signaling [ 34 ]. Moreover, the primary cilium, a sensory organelle with an exceptionally high receptor density [ 233 ], was shown to play a critical role in the de-differentiation process of adipose progenitors toward a CAF phenotype by mediating TGFβ signaling [ 234 ]. All these studies suggest that diverse pathways are responsible for the activation of CAFs, and the TME is likely the major player in triggering the de-differentiation of ASCs/MSCs into different CAFs, depending on their cellular context and the tumor entity.…”

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

“…For example, CAFs could contribute to tumor development by providing oxygen and suppressing the immune cells in the TME [ 10 ]. However, other studies suggest that CAFs can exert a tumor-suppressive impact on the TME [ 11 ]. For example, a previous study discovered that CAFs have a vital suppressive impact on fibrosarcoma [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Cancer-Associated Fibroblast Subtype of Triple-Negative Breast Cancer

Wang

Feng

Chen

et al. 2022

Journal of Oncology

View full text Add to dashboard Cite

Background. There is limited knowledge about the role of cancer-associated fibroblasts (CAF) in the tumor microenvironment of triple-negative breast cancer (TNBC). Methods. Three hundred and thirty-five TNBC samples from four datasets were retrieved and analyzed. In order to determine the CAF subtype by combining gene expression profiles, an unsupervised clustering analysis was adopted. The prognosis, enriched pathways, immune cells, immune scores, and tumor purity were compared between CAF subtypes. The genes with the highest importance were selected by bioinformatics analysis. The machine learning model was built to predict the TNBC CAF subtype by these selected genes. Results. TNBC samples were classified into two CAF subtypes (CAF+ and CAF-). The CAF- subtype of TNBC was linked to the longer overall survival and more immune cells than the CAF+ subtype. CAF- and CAF+ were enriched in immune-related pathways and extracellular matrix pathways, respectively. Bioinformatics analysis identified 9 CAF subtype-related markers (ADAMTS12, AEBP1, COL10A1, COL11A1, CXCL11, CXCR6, EDNRA, EPPK1, and WNT7B). We constructed a robust random forest model using these 9 genes, and the area under the curve (AUC) value of the model was 0.921. Conclusion. The current study identified CAF subtypes based on gene expression profiles and found that CAF subtypes have significantly different overall survival, immune cells, and immunotherapy response rates.

show abstract

The Primary Cilium of Adipose Progenitors Is Necessary for Their Differentiation into Cancer-Associated Fibroblasts that Promote Migration of Breast Cancer Cells In Vitro

Cited by 5 publications

References 46 publications

Identification of Human Breast Adipose Tissue Progenitors Displaying Distinct Differentiation Potentials and Interactions with Cancer Cells

Identification of Human Breast Adipose Tissue Progenitors Displaying Distinct Differentiation Potentials and Interactions with Cancer Cells

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

Identification of Cancer-Associated Fibroblast Subtype of Triple-Negative Breast Cancer

Contact Info

Product

Resources

About