The Role of Adipose-Derived Stem Cells in Breast Cancer Progression and Metastasis

Schweizer, Riccardo; Tsuji, Wakako; Gorantla, Vijay S.; Marra, Kacey G.; Rubin, J. Peter; Plock, Jan A.

doi:10.1155/2015/120949

Cited by 84 publications

(71 citation statements)

References 185 publications

(308 reference statements)

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“…The orchestration of cellular and humoral immune responses to self and foreign antigens can be disarranged by the interference of MSCs in the maturation, differentiation, and function of immune cells (Schweizer et al, 2015). Inducing a local immunosuppressive microenvironment, MSCs are capable of suppressing T cell and B cell proliferation (Augello et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Cancer and normal adipose‐derived mesenchymal stem cells (ASCs): Do they have differential effects on tumor and immune cells?

Razmkhah

Mansourabadi

Mohtasebi

et al. 2018

Cell Biology International

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Adipose-derived mesenchymal stem cells (ASCs) are known to have immunomodulatory properties through soluble factors or by direct cell-to-cell contact. This study aimed to assess the expression of HLA-G and IDO activity in breast cancer and normal ASCs and to see whether ASC is capable of modulating both tumor cells and immune system cells in vitro. ASCs were enzymatically isolated from 15 breast cancer patients and 10 normal individuals. Then they were cultured, and the impact of their conditioned media on the movement of the MDA-MB-231 breast cancer cell line was studied in wound healing scratch assay. Next, PBLs from the peripheral blood of normal individuals were separated and co-cultured with breast cancer and normal ASCs. PBLs proliferation and apoptosis were assessed using CFSE labeling dye and annexin V/7AAD staining, respectively. IDO activity and HLA-G protein expression in ASCs were examined using kynurenine assay and Western blotting, respectively. Tumor-derived ASCs, especially those from higher stages of breast cancer, have stronger effects on the proliferation and movement of MDA-MB-231 cells than normal ASCs (P-value < 0.05). Apoptosis in PBLs increased in the presence of ASCs compared to PBLs cultured alone (P-value < 0.05). In contrast, necrosis of PBLs decreased in the presence of ASCs compared to apoptosis in these cells (P-value < 0.001). Collectively, ASCs may have strategic effects on both tumor cells and cells of the immune system in the tumor microenvironment, resulting in tumor development, growth, and metastasis.

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Section: Discussionmentioning

confidence: 99%

Cancer and normal adipose‐derived mesenchymal stem cells (ASCs): Do they have differential effects on tumor and immune cells?

Razmkhah

Mansourabadi

Mohtasebi

et al. 2018

Cell Biology International

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“…However, emerging evidence indicates that ASCs may contribute to the growth and metastasis of breast cancer [25, 26]. Conversely, other studies have demonstrated an inhibitory role of ASCs in breast cancer [6, 7].…”

Section: Discussionmentioning

confidence: 99%

c-Kit-Positive Adipose Tissue-Derived Mesenchymal Stem Cells Promote the Growth and Angiogenesis of Breast Cancer

Cheng

2017

BioMed Research International

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Background Adipose tissue-derived mesenchymal stem cells (ASCs) improve the regenerative ability and retention of fat grafts for breast reconstruction in cancer patients following mastectomy. However, ASCs have also been shown to promote breast cancer cell growth and metastasis. For the safety of ASC application, we aimed to identify specific markers for the subpopulation of ASCs that enhance the growth of breast cancer. Methods ASCs and bone marrow-derived vascular endothelial progenitor cells (EPCs) were isolated from Balb/c mice. c-Kit-positive (c-Kit+) or c-Kit-negative (c-Kit−) ASCs were cocultured with 4T1 breast cancer cells. Orthotropic murine models of 4T1, EPCs + 4T1, and c-Kit+/-ASCs + 4T1/EPCs were established in Balb/c mice. Results In coculture, c-Kit+ ASCs enhanced the viability and proliferation of 4T1 cells and stimulated c-Kit expression and interleukin-3 (IL-3) release. In mouse models, c-Kit+ASCs + 4T1/EPCs coinjection increased the tumor volume and vessel formation. Moreover, IL-3, stromal cell-derived factor-1, and vascular endothelial growth factor A in the c-Kit+ASCs + 4T1/EPCs coinjection group were higher than those in the 4T1, EPCs + 4T1, and c-Kit−ASCs + 4T1/EPCs groups. Conclusions c-Kit+ ASCs may promote breast cancer growth and angiogenesis by a synergistic effect of c-Kit and IL-3. Our findings suggest that c-Kit+ subpopulations of ASCs should be eliminated in fat grafts for breast reconstruction of cancer patients following mastectomy.

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“…Adipose-tissue derived stem cells were reported to promote tumor growth (12). In our previous study, we have shown that expression of genes involved in cancer, cellular growth, proliferation and cellular movement changed significantly with polyploidization of ASCs (13).…”

Section: Ascb6 Increases Breast Cancer Progression and Metastasismentioning

confidence: 96%

“…An emerging problem with the ex vivo expanded stem cells is that they show chromosomal instabilities (7)(8)(9), which may be associated with cancer. Moreover, ASCs have been shown to integrate into tumor microenvironment, where they may promote the tumor progression by direct cell-cell contact or paracrine factors (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Polyploid Adipose Stem Cells Shift the Balance of IGF1/IGFBP2 to Promote the Growth of Breast Cancer

et al. 2020

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Background: The close proximity of adipose tissue and mammary epithelium predispose involvement of adipose cells in breast cancer development. Adipose-tissue stem cells (ASCs) contribute to tumor stroma and promote growth of cancer cells. In our previous study, we have shown that murine ASCs, which undergo polyploidization during their prolonged in vitro culturing, enhanced the proliferation of 4T1 murine breast cancer cells in IGF1 dependent manner.Aims: In the present study, our aim was to clarify the regulation of ASC-derived IGF1.Methods: 4T1 murine breast carcinoma cells were co-transplanted with visceral fat-derived ASCs (vASC) or with the polyploid ASC.B6 cell line into female BALB/c mice and tumor growth and lung metastasis were monitored. The conditioned media of vASCs and ASC.B6 cells were subjected to LC-MS/MS analysis and the production of IGFBP2 was verified by Western blotting. The regulatory effect was examined by adding recombinant IGFBP2 to the co-culture of ASC.B6 and 4T1. Akt/protein kinase B (PKB) activation was detected by Western blotting.Results: Polyploid ASCs promoted the tumor growth and metastasis more potently than vASCs with normal karyotype. vASCs produced the IGF1 regulator IGFBP2, which inhibited proliferation of 4T1 cells. Downregulation of IGFBP2 by polyploidization of ASCs and enhanced secretion of IGF1 allowed survival signaling in 4T1 cells, leading to Akt phosphorylation. Conclusions:Our results implicate that ASCs in the tumor microenvironment actively regulate the growth of breast cancer cells through the IGF/IGFBP system. Keywords: adipose stem cells, breast cancer, tumor stroma, insulin-like growth factor 1, insulin-like growth factor binding protein 2

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The Role of Adipose-Derived Stem Cells in Breast Cancer Progression and Metastasis

Cited by 84 publications

References 185 publications

Cancer and normal adipose‐derived mesenchymal stem cells (ASCs): Do they have differential effects on tumor and immune cells?

Cancer and normal adipose‐derived mesenchymal stem cells (ASCs): Do they have differential effects on tumor and immune cells?

c-Kit-Positive Adipose Tissue-Derived Mesenchymal Stem Cells Promote the Growth and Angiogenesis of Breast Cancer

Polyploid Adipose Stem Cells Shift the Balance of IGF1/IGFBP2 to Promote the Growth of Breast Cancer

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