ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model

Yy, Wang; Hung, Amos C.; Wu, Yi-Chia; Lo, Steven; Chen, Yuk-Kwan; Hsieh, Ya‐Ching; Hu, Stephen Chu‐Sung; Hou, Ming‐Feng; Yuan, Shyng‐Shiou F.

doi:10.1038/s41598-022-19290-6

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…MIP-1alpha increased in the co-culture media when compared to ASC-L media alone, and MMP-3 increased in the co-culture media when compared to macrophage media alone. These are all cytokines that have been shown to increase tumor aggression [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

Interaction between Macrophages and Adipose Stromal Cells Increases the Angiogenic and Proliferative Potential of Pregnancy-Associated Breast Cancers

Doyle,

Kwami,

Joshi

et al. 2023

Cancers

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Pregnancy associated breast cancers (PABCs) exhibit increased aggressiveness and overall poorer survival. During lactation, changes take place in the breast tissue microenvironment that lead to increased macrophage recruitment and alterations in adipose stromal cells (ASC-Ls). The interaction of these cells in PABCs could play a role in the increased aggressiveness of these cancers. We utilized an in vitro co-culture model to recreate the interactions of ASC-Ls and macrophages in vivo. We performed qRT-PCR to observe changes in gene expression and cytokine arrays to identify transcriptional changes that result in an altered microenvironment. Additionally, functional assays were performed to further elicit how these changes affect tumorigenesis. The co-culture of ASC-Ls and macrophages altered both mRNA expression and cytokine secretion in a tumor promoting manner. Tumorigenic cytokines, such as IL-6, CXCL1, CXCL5, and MMP-9 secretion levels, were enhanced in the co-culture. Additionally, conditioned media from the co-culture elevated the tumor cell proliferation and angiogenic potential of endothelial cells. These finds indicate that the changes seen in the microenvironment of PABC, specifically the secretion of cytokines, play a role in the increased tumorigenesis of PABCs by altering the microenvironment to become more favorable to tumor progression.

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Section: Resultsmentioning

confidence: 99%

Interaction between Macrophages and Adipose Stromal Cells Increases the Angiogenic and Proliferative Potential of Pregnancy-Associated Breast Cancers

Doyle,

Kwami,

Joshi

et al. 2023

Cancers

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“…There have been reports that ADSCs promote an in ammatory environment conducive to the growth of breast cancer cells [34], and increase drug resistance [35]. However, reports of ADSCs inducing morphological changes in breast cancer cells within a collagen matrix have been scarce.…”

Section: Discussionmentioning

confidence: 99%

3D spheroid model of adipose-derived stem cell and breast cancer cell co- culture for mimicking cell migration and the cancer environment

Kim,

Bae

et al. 2023

Preprint

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Traditional two-dimensional (2D) cell culture methodologies exhibit significant limitations, notably their failure to replicate the intricate three-dimensional (3D) milieu of human tissue architecture. This discrepancy has catalyzed the exploration of advanced drug screening platforms that more faithfully mimic the complex 3D biological environment. To this end, precision medicine research has increasingly used 3D in vitro models that emulate the tissue microenvironment of the human body. In this study, breast cancer cell lines (MDA-MB-231 and SK-BR-3) were co-cultured with adipose-derived stem cells (ADSCs), mimicking the in vitro 3D tumor microenvironment with the multicellular and heterogeneous nature of solid tumors compared to a 2D cancer cell only system. Additionally, collagen type I was used to replicate the microenvironment within a 3D spheroid platform, enhancing the accuracy of the platform in mimicking human tissue characteristics. Significantly, the interactions between the ADSCs and two breast cancer lines markedly influenced factors such as cell elongation, molecular expression, migration patterns, and drug sensitivity. The integration of ADSCs was pivotal in simulating the cancer microenvironment, highlighting that even within the same cancer cell line, varying microenvironmental contexts can lead to vastly different experimental results. Thus, this study provides insights into the role of factors such as cellular substrates and stem cells in simulating a 3D tumor microenvironment more akin to the human body when constructing a 3D in vitro system based on breast cancer cells.

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“…Total protein extracted from OSCC cells was analyzed using the Human Phospho Kinase Array (R&D Systems, Minneapolis, MN, USA), according to the manufacturer’s instructions and our previous reports [ 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway

et al. 2023

Self Cite

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Background Interleukin-1 receptor antagonist (IL-1RA), a member of the IL-1 family, has diverse roles in cancer development. However, the role of IL-1RA in oral squamous cell carcinoma (OSCC), in particular the underlying mechanisms, remains to be elucidated. Methods Tumor tissues from OSCC patients were assessed for protein expression by immunohistochemistry. Patient survival was evaluated by Kaplan–Meier curve analysis. Impact of differential IL-1RA expression on cultured OSCC cell lines was assessed in vitro by clonogenic survival, tumorsphere formation, soft agar colony formation, and transwell cell migration and invasion assays. Oxygen consumption rate was measured by Seahorse analyzer or multi-mode plate reader. PCR array was applied to screen human cancer stem cell-related genes, proteome array for phosphorylation status of kinases, and Western blot for protein expression in cultured cells. In vivo tumor growth was investigated by orthotopic xenograft in mice, and protein expression in xenograft tumors assessed by immunohistochemistry. Results Clinical analysis revealed that elevated IL-1RA expression in OSCC tumor tissues was associated with increased tumor size and cancer stage, and reduced survival in the patient group receiving adjuvant radiotherapy compared to the patient group without adjuvant radiotherapy. In vitro data supported these observations, showing that overexpression of IL-1RA increased OSCC cell growth, migration/invasion abilities, and resistance to ionizing radiation, whereas knockdown of IL-1RA had largely the opposite effects. Additionally, we identified that EGFR/JNK activation and SOX2 expression were modulated by differential IL-1RA expression downstream of mitochondrial metabolism, with application of mitochondrial complex inhibitors suppressing these pathways. Furthermore, in vivo data revealed that treatment with cisplatin or metformin—a mitochondrial complex inhibitor and conventional therapy for type 2 diabetes—reduced IL-1RA-associated xenograft tumor growth as well as EGFR/JNK activation and SOX2 expression. This inhibitory effect was further augmented by combination treatment with cisplatin and metformin. Conclusions The current study suggests that IL-1RA promoted OSCC malignancy through mitochondrial metabolism-mediated EGFR/JNK activation and SOX2 expression. Inhibition of this mitochondrial metabolic pathway may present a potential therapeutic strategy in OSCC.

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ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model

Cited by 6 publications

References 49 publications

Interaction between Macrophages and Adipose Stromal Cells Increases the Angiogenic and Proliferative Potential of Pregnancy-Associated Breast Cancers

Interaction between Macrophages and Adipose Stromal Cells Increases the Angiogenic and Proliferative Potential of Pregnancy-Associated Breast Cancers

3D spheroid model of adipose-derived stem cell and breast cancer cell co- culture for mimicking cell migration and the cancer environment

IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway

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