PMID- 35927653 OWN - NLM STAT- MEDLINE DCOM- 20220808 LR - 20231101 IS - 1476-511X (Electronic) IS - 1476-511X (Linking) VI - 21 IP - 1 DP - 2022 Aug 4 TI - Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity. PG - 67 LID - 10.1186/s12944-022-01678-y [doi] LID - 67 AB - 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. CI - (c) 2022. The Author(s). FAU - Ibrahim, Aya Saber AU - Ibrahim AS AD - Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt. ayas@sci.cu.edu.eg. FAU - El-Shinawi, Mohamed AU - El-Shinawi M AD - Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo, 11566, Egypt. AD - International Affairs, Galala University, Suez, Egypt. FAU - Sabet, Salwa AU - Sabet S AD - Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt. FAU - Ibrahim, Sherif Abdelaziz AU - Ibrahim SA AD - Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt. FAU - Mohamed, Mona Mostafa AU - Mohamed MM AD - Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt. AD - Molecular Biotechnology Program, Faculty of Science, Galala University, Suez, Egypt. LA - eng PT - Journal Article DEP - 20220804 PL - England TA - Lipids Health Dis JT - Lipids in health and disease JID - 101147696 RN - 0 (Adipokines) RN - 0 (Cadherins) RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) SB - IM MH - Adipokines/genetics MH - Adipose Tissue/metabolism MH - *Breast Neoplasms/genetics/pathology MH - Cadherins MH - Cell Line, Tumor MH - Cytokines/genetics MH - Female MH - Humans MH - *Inflammatory Breast Neoplasms/genetics/metabolism/pathology MH - Interleukin-6/genetics/metabolism MH - Interleukin-8 MH - Obesity/complications/genetics PMC - PMC9351154 OTO - NOTNLM OT - Breast cancer stem cells OT - Cancer-associated adipose tissue OT - EMT OT - Inflammatory breast cancer OT - Interleukin-6 OT - Interleukin-8 OT - Monocyte chemo-attractant protein-1 OT - Obesity COIS- The authors declare that they have no competing interests. EDAT- 2022/08/05 06:00 MHDA- 2022/08/09 06:00 PMCR- 2022/08/04 CRDT- 2022/08/04 23:44 PHST- 2022/03/02 00:00 [received] PHST- 2022/07/13 00:00 [accepted] PHST- 2022/08/04 23:44 [entrez] PHST- 2022/08/05 06:00 [pubmed] PHST- 2022/08/09 06:00 [medline] PHST- 2022/08/04 00:00 [pmc-release] AID - 10.1186/s12944-022-01678-y [pii] AID - 1678 [pii] AID - 10.1186/s12944-022-01678-y [doi] PST - epublish SO - Lipids Health Dis. 2022 Aug 4;21(1):67. doi: 10.1186/s12944-022-01678-y.