Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity
Abstract Background Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different ce...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Lipids in Health and Disease |
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| Online Access: | https://doi.org/10.1186/s12944-022-01678-y |
| _version_ | 1811315380516290560 |
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| author | Aya Saber Ibrahim Mohamed El-Shinawi Salwa Sabet Sherif Abdelaziz Ibrahim Mona Mostafa Mohamed |
| author_facet | Aya Saber Ibrahim Mohamed El-Shinawi Salwa Sabet Sherif Abdelaziz Ibrahim Mona Mostafa Mohamed |
| author_sort | Aya Saber Ibrahim |
| collection | DOAJ |
| description | Abstract Background Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease. Methods This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student’s t-test. Results The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell. Conclusions This study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC. |
| first_indexed | 2024-04-13T11:29:17Z |
| format | Article |
| id | doaj.art-0442bcb8a29a43a8876b268c866614d4 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-04-13T11:29:17Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-0442bcb8a29a43a8876b268c866614d42022-12-22T02:48:36ZengBMCLipids in Health and Disease1476-511X2022-08-0121111310.1186/s12944-022-01678-yRole of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesityAya Saber Ibrahim0Mohamed El-Shinawi1Salwa Sabet2Sherif Abdelaziz Ibrahim3Mona Mostafa Mohamed4Zoology Department, Faculty of Science, Cairo UniversityDepartment of General Surgery, Faculty of Medicine, Ain Shams UniversityZoology Department, Faculty of Science, Cairo UniversityZoology Department, Faculty of Science, Cairo UniversityZoology Department, Faculty of Science, Cairo UniversityAbstract Background Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease. Methods This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student’s t-test. Results The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell. Conclusions This study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC.https://doi.org/10.1186/s12944-022-01678-yInflammatory breast cancerCancer-associated adipose tissueObesityInterleukin-6Interleukin-8Monocyte chemo-attractant protein-1 |
| spellingShingle | Aya Saber Ibrahim Mohamed El-Shinawi Salwa Sabet Sherif Abdelaziz Ibrahim Mona Mostafa Mohamed Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity Lipids in Health and Disease Inflammatory breast cancer Cancer-associated adipose tissue Obesity Interleukin-6 Interleukin-8 Monocyte chemo-attractant protein-1 |
| title | Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity |
| title_full | Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity |
| title_fullStr | Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity |
| title_full_unstemmed | Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity |
| title_short | Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity |
| title_sort | role of adipose tissue derived cytokines in the progression of inflammatory breast cancer in patients with obesity |
| topic | Inflammatory breast cancer Cancer-associated adipose tissue Obesity Interleukin-6 Interleukin-8 Monocyte chemo-attractant protein-1 |
| url | https://doi.org/10.1186/s12944-022-01678-y |
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