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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

IL-6 mediates ADSC-induced growth of breast and colon cancer cells(A) Cell growth of 4T1 and CT26 cells grown alone or in co-culture with ADSCs was assessed by cell counting. Neutralizing antibody against IL-6 (Anti-IL-6) was additional added to the co-cultures of ADSCs with cancer cells. Values are means + SEM; *, P<0.05; ***, P<0.001 in unpaired t-tests with Welch's correction. (B) mRNA levels of MKI67 and PCNA were determined by RT-PCR in 4T1 or CT26 cells with different conditions. Values (means + SEM) are normalized to GAPDH loading and are relative to levels of 4T1 or CT26 alone respectively; *, P<0.05; **, P<0.01 using paired t-tests.
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Figure 6: IL-6 mediates ADSC-induced growth of breast and colon cancer cells(A) Cell growth of 4T1 and CT26 cells grown alone or in co-culture with ADSCs was assessed by cell counting. Neutralizing antibody against IL-6 (Anti-IL-6) was additional added to the co-cultures of ADSCs with cancer cells. Values are means + SEM; *, P<0.05; ***, P<0.001 in unpaired t-tests with Welch's correction. (B) mRNA levels of MKI67 and PCNA were determined by RT-PCR in 4T1 or CT26 cells with different conditions. Values (means + SEM) are normalized to GAPDH loading and are relative to levels of 4T1 or CT26 alone respectively; *, P<0.05; **, P<0.01 using paired t-tests.

Mentions: To determine the contribution of IL-6 in mediating the ADSC-enhanced malignant characteristics of cancer cells, we utilized antibody to neutralize the function of IL-6. First, we examined the effects of IL-6 on tumor-initiating properties of breast and colon cancer cells. Parallel to the previous results, the number of tumor sphere was increased when co-cultured with ADSCs. But the ADSC-enhanced sphere generation of breast and colon cancer cells was significantly reduced by IL-6–neutralized antibodies (Figure 5A). We then utilized semiquantitative RT-PCR analysis to determine the effects of IL-6–neutralized antibodies on CSC markers. The expressions of self-renewal-related genes, including SOX2 (4T1, 21.26 ± 3.06; CT26, 6.39 ± 0.82) and NANOG (4T1, 2.38 ± 0.86; CT26, 3.36 ± 0.72), and drug resistance-related genes, including ALDH1A1 (4T1, 3.98 ± 0.55; CT26, 18.9 ± 4.59) and ABCG2 (4T1, 1.55 ± 0.15; CT26, 1.96 ± 0.57), were relatively increased in cancer cells after co-culture with ADSCs. As expected, IL-6–neutralized antibodies markedly diminished the ADSCs-induced up-regulation of these genes in cancer cells, including SOX2 (4T1, 0.87 ± 0.12; CT26, 1.24 ± 0.41), NANOG (4T1, 0.85 ± 0.33; CT26, 2.35 ± 0.64), ALDH1A1 (4T1, 0.6 ± 0.34; CT26, 3.8 ± 0.88), and ABCG2 (4T1, 0.95 ± 0.08; CT26, 0.96 ± 0.24) (Figure 5B). We then evaluated the effects of IL-6 on the growth abilities of cancer cells. As shown in Figure 6A, the ADSC-enhanced cell growth of cancer cells was significantly suppressed by IL-6–neutralized antibodies. Similar to the results of CSC marker genes, semiquantitative RT-PCR analysis showed that ADSCs strongly upregulate the growth-related genes in cancer cells, including MKI67 (4T1, 7.44 ± 2.43; CT26, 2.93 ± 0.29) and PCNA (4T1, 3.85 ± 1.02; CT26, 7.09 ± 1.54). We also found that IL-6 neutralization markedly diminished the up-regulation of MKI67 (4T1, 1.21 ± 0.22; CT26, 1.27 ± 0.31) and PCNA (4T1, 1.54 ± 0.9; CT26, 1.20 ± 0.46) induced by ADSCs in cancer cells (Figure 6B). Collectively, these results indicate that IL-6 as a key regulator that contributes to the ADSCs-induced enhancement of tumor-initiating properties and growth abilities in both breast and colon cancer cells.


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)

IL-6 mediates ADSC-induced growth of breast and colon cancer cells(A) Cell growth of 4T1 and CT26 cells grown alone or in co-culture with ADSCs was assessed by cell counting. Neutralizing antibody against IL-6 (Anti-IL-6) was additional added to the co-cultures of ADSCs with cancer cells. Values are means + SEM; *, P<0.05; ***, P<0.001 in unpaired t-tests with Welch's correction. (B) mRNA levels of MKI67 and PCNA were determined by RT-PCR in 4T1 or CT26 cells with different conditions. Values (means + SEM) are normalized to GAPDH loading and are relative to levels of 4T1 or CT26 alone respectively; *, P<0.05; **, P<0.01 using paired t-tests.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 6: IL-6 mediates ADSC-induced growth of breast and colon cancer cells(A) Cell growth of 4T1 and CT26 cells grown alone or in co-culture with ADSCs was assessed by cell counting. Neutralizing antibody against IL-6 (Anti-IL-6) was additional added to the co-cultures of ADSCs with cancer cells. Values are means + SEM; *, P<0.05; ***, P<0.001 in unpaired t-tests with Welch's correction. (B) mRNA levels of MKI67 and PCNA were determined by RT-PCR in 4T1 or CT26 cells with different conditions. Values (means + SEM) are normalized to GAPDH loading and are relative to levels of 4T1 or CT26 alone respectively; *, P<0.05; **, P<0.01 using paired t-tests.
Mentions: To determine the contribution of IL-6 in mediating the ADSC-enhanced malignant characteristics of cancer cells, we utilized antibody to neutralize the function of IL-6. First, we examined the effects of IL-6 on tumor-initiating properties of breast and colon cancer cells. Parallel to the previous results, the number of tumor sphere was increased when co-cultured with ADSCs. But the ADSC-enhanced sphere generation of breast and colon cancer cells was significantly reduced by IL-6–neutralized antibodies (Figure 5A). We then utilized semiquantitative RT-PCR analysis to determine the effects of IL-6–neutralized antibodies on CSC markers. The expressions of self-renewal-related genes, including SOX2 (4T1, 21.26 ± 3.06; CT26, 6.39 ± 0.82) and NANOG (4T1, 2.38 ± 0.86; CT26, 3.36 ± 0.72), and drug resistance-related genes, including ALDH1A1 (4T1, 3.98 ± 0.55; CT26, 18.9 ± 4.59) and ABCG2 (4T1, 1.55 ± 0.15; CT26, 1.96 ± 0.57), were relatively increased in cancer cells after co-culture with ADSCs. As expected, IL-6–neutralized antibodies markedly diminished the ADSCs-induced up-regulation of these genes in cancer cells, including SOX2 (4T1, 0.87 ± 0.12; CT26, 1.24 ± 0.41), NANOG (4T1, 0.85 ± 0.33; CT26, 2.35 ± 0.64), ALDH1A1 (4T1, 0.6 ± 0.34; CT26, 3.8 ± 0.88), and ABCG2 (4T1, 0.95 ± 0.08; CT26, 0.96 ± 0.24) (Figure 5B). We then evaluated the effects of IL-6 on the growth abilities of cancer cells. As shown in Figure 6A, the ADSC-enhanced cell growth of cancer cells was significantly suppressed by IL-6–neutralized antibodies. Similar to the results of CSC marker genes, semiquantitative RT-PCR analysis showed that ADSCs strongly upregulate the growth-related genes in cancer cells, including MKI67 (4T1, 7.44 ± 2.43; CT26, 2.93 ± 0.29) and PCNA (4T1, 3.85 ± 1.02; CT26, 7.09 ± 1.54). We also found that IL-6 neutralization markedly diminished the up-regulation of MKI67 (4T1, 1.21 ± 0.22; CT26, 1.27 ± 0.31) and PCNA (4T1, 1.54 ± 0.9; CT26, 1.20 ± 0.46) induced by ADSCs in cancer cells (Figure 6B). Collectively, these results indicate that IL-6 as a key regulator that contributes to the ADSCs-induced enhancement of tumor-initiating properties and growth abilities in both breast and colon cancer cells.

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