Co-culture With Human Breast Adipocytes Differentially Regulates Protein Abundance in Breast Cancer Cells

Crake, Rebekah; Phillips, Elisabeth; Kleffmann, Torsten; Currie, Margaret J.

doi:10.21873/cgp.20137

Cited by 10 publications

(6 citation statements)

References 62 publications

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“…In the literature, the expression of CPT1A, ABCG1, SREBF1 and LGALS3BP has been associated with obesity (50-54) and linked to various cancers (55)(56)(57)(58)(59)(60)(61)(62), including breast cancer (63-69) adding plausibility to the findings. Indeed, CPT1A was recently found to be up-regulated in co-cultured adipocytes isolated from human breast adipose tissue with hormone receptor-positive or -negative breast cancer cells (70). Altogether, these findings support the notion that BMI is associated with the expression of CPT1A, ABCG1, SREBF1 and LGALS3BP in normal tissue among breast cancer patients.…”

Section: Discussionsupporting

confidence: 71%

Association Between BMI and DNA Methylation in Blood or Normal Adult Breast Tissue: A Systematic Review

et al. 2020

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Background/Aim: Several studies have investigated the influence of obesity on DNA methylation (DNAm) to find biomarkers associated with the detection of chronic diseases, including breast cancer. The aim of the study was to systematically review studies examining the association of body mass index (BMI) and DNAm in blood or normal breast tissue. Materials and Methods: Three scientific literature databases (PubMed, Embase and Web of Science) were screened until May 2018. Results: Twenty-four studies were included along with ours in which we investigated this relation in the normal breast tissue of 40 breast cancer patients. Conclusion: BMIassociated CpG sites were highly variable with few identified in less than half of the studies. Nevertheless, a few genes potentially associated with BMI were highlighted in blood (CPT1A, ABCG1, SREBF1 and LGALS3BP) and in normal breast tissue (PTPRN2 and ABLIM2). The variability of the results could be explained by the tissue and cell-specificity of methylation and differences in methodology.

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Section: Discussionsupporting

confidence: 71%

Association Between BMI and DNA Methylation in Blood or Normal Adult Breast Tissue: A Systematic Review

et al. 2020

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“…Emerging evidence suggests that adipocytes participate in intimate mutual and dynamic crosstalk with cancer cells and promote cancer cell migration, invasion and metastasis and drug resistance [ 25 , 46 ]. Influenced by cancer cells, NAs are driven to become CAAs, which are characterized by a fibroblast-like phenotype, reduced differentiation capacity, and the presence of small fat droplets [ 47 ]. In this process of transformation, CAAs gradually lose their differentiation capacity through the downregulation of markers associated with adipose differentiation, such as FABP4 and adiponectin [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting cancer-associated adipocyte-derived CXCL8 inhibits triple-negative breast cancer progression and enhances the efficacy of anti-PD-1 immunotherapy

Huang,

Wang,

Hong

et al. 2023

Cell Death Dis

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Cancer-associated adipocytes (CAAs), one of the primary stromal components, exhibit intimate crosstalk and release multiple cell factors mediating local and systemic biological effects. However, the role of CAAs in the regulation of systemic immune responses and their potential value in the clinical treatment of triple-negative breast cancer (TNBC) are not well described. Transcriptome sequencing was performed on CAA and normal adipocyte (NA) tissues isolated from surgically resected samples from TNBC patients and healthy controls. Cytokines, including C-X-C motif chemokine ligand 8 (CXCL8, also known as IL-8), secreted from NAs and CAAs were compared by transcriptome sequencing and enzyme-linked immunosorbent assay (ELISA). Proliferation, migration and invasion assays were employed to analyze the role of CAAs and CAA-derived CXCL8 (macrophage inflammatory protein-2 (MIP2) as a functional surrogate in mice). TNBC syngraft models were established to evaluate the curative effect of targeting CXCL8 in combination with anti-PD-1 therapies. Real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), polymerase chain reaction (PCR) array, flow cytometry, immunohistochemistry (IHC), and immunofluorescence (IF) were applied to analyze immune cell infiltration and epithelial–mesenchymal transition (EMT) markers. Specifically, we demonstrated that CAAs and CAA-derived CXCL8 played important roles in tumor growth, EMT, metastasis and tumor immunity suppression. CAA-derived CXCL8 remodeled the tumor immune microenvironment not only by suppressing CD4+ T and CD8+ T immune cell infiltration but also by upregulating CD274 expression in TNBC. The combination of targeting the CXCL8 pathway and blocking the PD-1 pathway synergistically increased the tumor immune response and inhibited tumor progression. Thus, our results highlight the molecular mechanisms and translational significance of CAAs in tumor progression and immune ecosystem regulatory effects and provide a better understanding of the potential clinical benefit of targeting CAA-derived CXCL8 in antitumor immunity and as a new therapeutic moiety in TNBC.

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“…Modern top-down and bottom-up MS-based proteomic techniques, especially those based on MALDI-ToF MS and LC–MS/MS, allowed for understanding of proteomic differences between cancer-associated fibroblasts (CAFs) and their normal fibroblast counterpart; the metabolic reprogramming associated with fibroblast activation; the reciprocal metabolic cross-talk between CAFs and cancer cells that involves the identification of CAF-derived proteins which act as regulators of cancer cell proliferation as well as the contribute to the CAFs secretome; these represent some among a long list of other ECM proteins that interact or remodel ECM, which leads to a complex proteomic profile of tumor matrisome [ 127 , 128 ]. To demonstrate the role of cancer-associated adipocytes (CAAs) in breast cancer cell migration, invasion, and resistance to therapy, DEPs in BC cells co-cultured with CAAs isolated from human breast adipose tissue have been identified and quantified using iTRAQ labelling and LC–MS/MS [ 129 ]. Pathway analysis demonstrated that CAAs emphasized a paracrine role in the enrichment of proteins involved in metabolism, ubiquitin proteasome, and purine synthesis.…”

Section: Proteomics-based Investigation Of Dysregulated Proteins Proc...mentioning

confidence: 99%

Proteomics-Based Identification of Dysregulated Proteins and Biomarker Discovery in Invasive Ductal Carcinoma, the Most Common Breast Cancer Subtype

et al. 2023

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Invasive ductal carcinoma (IDC) is the most common histological subtype of malignant breast cancer (BC), and accounts for 70–80% of all invasive BCs. IDC demonstrates great heterogeneity in clinical and histopathological characteristics, prognoses, treatment strategies, gene expressions, and proteomic profiles. Significant proteomic determinants of the progression from intraductal pre-invasive malignant lesions of the breast, which characterize a ductal carcinoma in situ (DCIS), to IDC, are still poorly identified, validated, and clinically applied. In the era of “6P” medicine, it remains a great challenge to determine which patients should be over-treated versus which need to be actively monitored without aggressive treatment. The major difficulties for designating DCIS to IDC progression may be solved by understanding the integrated genomic, transcriptomic, and proteomic bases of invasion. In this review, we showed that multiple proteomics-based techniques, such as LC–MS/MS, MALDI-ToF MS, SELDI-ToF-MS, MALDI-ToF/ToF MS, MALDI-MSI or MasSpec Pen, applied to in-tissue, off-tissue, BC cell lines and liquid biopsies, improve the diagnosis of IDC, as well as its prognosis and treatment monitoring. Classic proteomics strategies that allow the identification of dysregulated protein expressions, biological processes, and interrelated pathway analyses based on aberrant protein–protein interaction (PPI) networks have been improved to perform non-invasive/minimally invasive biomarker detection of early-stage IDC. Thus, in modern surgical oncology, highly sensitive, rapid, and accurate MS-based detection has been coupled with “proteome point sampling” methods that allow for proteomic profiling by in vivo “proteome point characterization”, or by minimal tissue removal, for ex vivo accurate differentiation and delimitation of IDC. For the detection of low-molecular-weight proteins and protein fragments in bodily fluids, LC–MS/MS and MALDI-MS techniques may be coupled to enrich and capture methods which allow for the identification of early-stage IDC protein biomarkers that were previously invisible for MS-based techniques. Moreover, the detection and characterization of protein isoforms, including posttranslational modifications of proteins (PTMs), is also essential to emphasize specific molecular mechanisms, and to assure the early-stage detection of IDC of the breast.

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Co-culture With Human Breast Adipocytes Differentially Regulates Protein Abundance in Breast Cancer Cells

Cited by 10 publications

References 62 publications

Association Between BMI and DNA Methylation in Blood or Normal Adult Breast Tissue: A Systematic Review

Association Between BMI and DNA Methylation in Blood or Normal Adult Breast Tissue: A Systematic Review

Targeting cancer-associated adipocyte-derived CXCL8 inhibits triple-negative breast cancer progression and enhances the efficacy of anti-PD-1 immunotherapy

Proteomics-Based Identification of Dysregulated Proteins and Biomarker Discovery in Invasive Ductal Carcinoma, the Most Common Breast Cancer Subtype

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