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Adipose-derived stem cells promote tumor initiation and accelerate tumor growth by interleukin-6 production.

Wei HJ, Zeng R, Lu JH, Lai WF, Chen WH, Liu HY, Chang YT, Deng WP - Oncotarget (2015)

Bottom Line: Here, we show that ADSCs enhance sphere formation and in vivo tumor initiation of breast and colon cancer cells.ADSCs also accelerated tumor growth.We suggest that ADSCs may enhance tumor initiation and promotion.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.

ABSTRACT
Adipose-derived stem cells (ADSCs) are multipotent cells that have attracted much recent attention. Here, we show that ADSCs enhance sphere formation and in vivo tumor initiation of breast and colon cancer cells. In co-culture, ADSCs induced several stem cell markers in cancer cells. ADSCs also accelerated tumor growth. Interaction of ADSCs and cancer cells stimulated secretion of interlukin-6 in ADSCs, which in turn acted in a paracrine manner on cancer cells to enhance their malignant properties. Interleukin-6 regulated stem cell-related genes and activated JAK2/STAT3 in cancer cells. We suggest that ADSCs may enhance tumor initiation and promotion.

No MeSH data available.


Related in: MedlinePlus

Characterization of ADSCs from mouse abdominal adipose tissues(A) Cell-surface marker profiles of ADSCs determined by flow cytometry using antibodies against indicated antigens; grey regions represent isotype controls. Multilineage differentiation capacity of ADSCs was identified by (B) specific marker gene expression and (C) lineage-specific staining. Osteogenic differentiation was assessed by Alizarin Red S staining for mineral nodule deposition. Adipogenic differentiation was assessed by Oil Red O staining for lipid vesicle formation. Chondrogenic differentiation was assessed by Alcian blue staining for proteoglycan deposition. IM: induction medium.
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Figure 1: Characterization of ADSCs from mouse abdominal adipose tissues(A) Cell-surface marker profiles of ADSCs determined by flow cytometry using antibodies against indicated antigens; grey regions represent isotype controls. Multilineage differentiation capacity of ADSCs was identified by (B) specific marker gene expression and (C) lineage-specific staining. Osteogenic differentiation was assessed by Alizarin Red S staining for mineral nodule deposition. Adipogenic differentiation was assessed by Oil Red O staining for lipid vesicle formation. Chondrogenic differentiation was assessed by Alcian blue staining for proteoglycan deposition. IM: induction medium.

Mentions: Adipose tissue is considered a source of adult stem cells of mesenchymal lineage. To determine whether stromal cells isolated from mice abdominal fat exhibited stem cell properties and were ADSCs, we conducted assays for cell surface markers and multilineage differentiation. As shown in Figure 1A, the cell surface marker profiles of isolated cells revealed similar immunophenotypes to MSCs, which were negative for CD34 and CD45 (hematopoietic stem cell markers) and positive for CD105 and Sca-1 (MSC markers). A key characteristic of MSCs is multipotency. We therefore tested whether the isolated cells displayed multipotent differentiation capacity including osteogenic, adipogenic, and chondrogenic differentiation. These cells were cultured under standard induction conditions, and in vitro differentiation was monitored by specific gene expression and lineage-specific staining. RT-PCR analysis demonstrated that upon induction the isolated cells upregulatd the differentiation marker genes of three different lineages. These differentiation marker genes are OPN and RUNX2 for osteogenesis, PPARG and Leptin for adipogenesis, and COL2A1 and ACAN for chondrogenesis (Figure 1B). Parallel to gene expression results, lineage-specific staining showed that Alizarin Red S staining for osteogenic matrix, Oil Red-O staining for lipid droplet, and Alcian Blue staining for proteoglycan accumulation were strongly enhanced in isolated cells after induction (Figure 1C). These results indicate that cells derived from adipose tissue conserve key MSC characteristics, including specific surface markers and multipotent differentiation capacity, and are known as ADSCs.


Adipose-derived stem cells promote tumor initiation and accelerate tumor growth by interleukin-6 production.

Wei HJ, Zeng R, Lu JH, Lai WF, Chen WH, Liu HY, Chang YT, Deng WP - Oncotarget (2015)

Characterization of ADSCs from mouse abdominal adipose tissues(A) Cell-surface marker profiles of ADSCs determined by flow cytometry using antibodies against indicated antigens; grey regions represent isotype controls. Multilineage differentiation capacity of ADSCs was identified by (B) specific marker gene expression and (C) lineage-specific staining. Osteogenic differentiation was assessed by Alizarin Red S staining for mineral nodule deposition. Adipogenic differentiation was assessed by Oil Red O staining for lipid vesicle formation. Chondrogenic differentiation was assessed by Alcian blue staining for proteoglycan deposition. IM: induction medium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480711&req=5

Figure 1: Characterization of ADSCs from mouse abdominal adipose tissues(A) Cell-surface marker profiles of ADSCs determined by flow cytometry using antibodies against indicated antigens; grey regions represent isotype controls. Multilineage differentiation capacity of ADSCs was identified by (B) specific marker gene expression and (C) lineage-specific staining. Osteogenic differentiation was assessed by Alizarin Red S staining for mineral nodule deposition. Adipogenic differentiation was assessed by Oil Red O staining for lipid vesicle formation. Chondrogenic differentiation was assessed by Alcian blue staining for proteoglycan deposition. IM: induction medium.
Mentions: Adipose tissue is considered a source of adult stem cells of mesenchymal lineage. To determine whether stromal cells isolated from mice abdominal fat exhibited stem cell properties and were ADSCs, we conducted assays for cell surface markers and multilineage differentiation. As shown in Figure 1A, the cell surface marker profiles of isolated cells revealed similar immunophenotypes to MSCs, which were negative for CD34 and CD45 (hematopoietic stem cell markers) and positive for CD105 and Sca-1 (MSC markers). A key characteristic of MSCs is multipotency. We therefore tested whether the isolated cells displayed multipotent differentiation capacity including osteogenic, adipogenic, and chondrogenic differentiation. These cells were cultured under standard induction conditions, and in vitro differentiation was monitored by specific gene expression and lineage-specific staining. RT-PCR analysis demonstrated that upon induction the isolated cells upregulatd the differentiation marker genes of three different lineages. These differentiation marker genes are OPN and RUNX2 for osteogenesis, PPARG and Leptin for adipogenesis, and COL2A1 and ACAN for chondrogenesis (Figure 1B). Parallel to gene expression results, lineage-specific staining showed that Alizarin Red S staining for osteogenic matrix, Oil Red-O staining for lipid droplet, and Alcian Blue staining for proteoglycan accumulation were strongly enhanced in isolated cells after induction (Figure 1C). These results indicate that cells derived from adipose tissue conserve key MSC characteristics, including specific surface markers and multipotent differentiation capacity, and are known as ADSCs.

Bottom Line: Here, we show that ADSCs enhance sphere formation and in vivo tumor initiation of breast and colon cancer cells.ADSCs also accelerated tumor growth.We suggest that ADSCs may enhance tumor initiation and promotion.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.

ABSTRACT
Adipose-derived stem cells (ADSCs) are multipotent cells that have attracted much recent attention. Here, we show that ADSCs enhance sphere formation and in vivo tumor initiation of breast and colon cancer cells. In co-culture, ADSCs induced several stem cell markers in cancer cells. ADSCs also accelerated tumor growth. Interaction of ADSCs and cancer cells stimulated secretion of interlukin-6 in ADSCs, which in turn acted in a paracrine manner on cancer cells to enhance their malignant properties. Interleukin-6 regulated stem cell-related genes and activated JAK2/STAT3 in cancer cells. We suggest that ADSCs may enhance tumor initiation and promotion.

No MeSH data available.


Related in: MedlinePlus