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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

ADSCs accelerate breast and colon cancer cell growth both in vitro and in vivo(A) In vitro cell growth of 4T1 and CT26 cells co-cultured directly with or without ADSCs assessed by bioluminescence assay. Values are means + SEM; *, P<0.05; **, P<0.01 in unpaired t test with Welch's correction. (B) In vitro cell growth measured by cell counting of 4T1 and CT26 cells co-cultured indirectly with or without ADSCs using trans-well. Values are means + SEM; *** indicates P<0.001 using unpaired t test with Welch's correction. (C) RT-PCR of MKI67 and PCNA expression in 4T1 and CT26 cells, with GAPDH as loading control. (D) Representative bioluminescence images and (E) tumour volume measurements (mean ± SEM) of 3 × 105 4T1 cells or 1.5 × 105 CT26 cells injected subcutaneously into syngeneic mice alone with or without five folds of ADSCs. Results were taken 0, 7, 14, and 21 days after implantation; *, P<0.05 in two-way ANOVA.
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Figure 3: ADSCs accelerate breast and colon cancer cell growth both in vitro and in vivo(A) In vitro cell growth of 4T1 and CT26 cells co-cultured directly with or without ADSCs assessed by bioluminescence assay. Values are means + SEM; *, P<0.05; **, P<0.01 in unpaired t test with Welch's correction. (B) In vitro cell growth measured by cell counting of 4T1 and CT26 cells co-cultured indirectly with or without ADSCs using trans-well. Values are means + SEM; *** indicates P<0.001 using unpaired t test with Welch's correction. (C) RT-PCR of MKI67 and PCNA expression in 4T1 and CT26 cells, with GAPDH as loading control. (D) Representative bioluminescence images and (E) tumour volume measurements (mean ± SEM) of 3 × 105 4T1 cells or 1.5 × 105 CT26 cells injected subcutaneously into syngeneic mice alone with or without five folds of ADSCs. Results were taken 0, 7, 14, and 21 days after implantation; *, P<0.05 in two-way ANOVA.

Mentions: To investigate whether the cell growth of breast and colon cancer cells was influenced by ADSCs, we directly co-cultured ADSCs with 4T1 or CT26 cells. The amount of cancer cells was evaluated by in vitro bioluminescent quantification. The bioluminescence activity was strongly enhanced in cancer cells co-cultured with ADSCs compared to cancer cells alone (Figure 3A), suggesting that ADSCs could increase the number of both cancer cells. ADSCs are known as a rich source of cytokines and chemokines, which can communicate with other surrounding cells in a paracrine manner. To further determine whether ADSCs enhanced cancer cell growth via paracrine effect, we co-cultured cancer cells with ADSCs indirectly using trans-well co-culture system. Consistent with above result, ADSCs could increase the cell number of breast and colon cancer cells upon co-culture with them (Figure 3B). We further found that ADSCs could upregulate the mRNA expression of proliferation-related genes in cancer cells, including MKI67 and PCNA (Figure 3C). We then utilized syngeneic tumor models to evaluate whether the in vivo tumor growth of cancer cells were influenced by ADSCs. BALB/c mice were injected 5 × 105 4T1 or 1.5 × 105 CT26 cancer cells with ADSCs subcutaneously. The tumor growth rate was evaluated by bioluminescent imaging and volume calculation. Representative images are shown in Figure 3D, and the results of tumor volume calculation are shown in Figure 3E. These data suggest that ADSCs significantly accelerate the growth rate of breast and colon cancer cells both in cell culture and in mice.


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)

ADSCs accelerate breast and colon cancer cell growth both in vitro and in vivo(A) In vitro cell growth of 4T1 and CT26 cells co-cultured directly with or without ADSCs assessed by bioluminescence assay. Values are means + SEM; *, P<0.05; **, P<0.01 in unpaired t test with Welch's correction. (B) In vitro cell growth measured by cell counting of 4T1 and CT26 cells co-cultured indirectly with or without ADSCs using trans-well. Values are means + SEM; *** indicates P<0.001 using unpaired t test with Welch's correction. (C) RT-PCR of MKI67 and PCNA expression in 4T1 and CT26 cells, with GAPDH as loading control. (D) Representative bioluminescence images and (E) tumour volume measurements (mean ± SEM) of 3 × 105 4T1 cells or 1.5 × 105 CT26 cells injected subcutaneously into syngeneic mice alone with or without five folds of ADSCs. Results were taken 0, 7, 14, and 21 days after implantation; *, P<0.05 in two-way ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: ADSCs accelerate breast and colon cancer cell growth both in vitro and in vivo(A) In vitro cell growth of 4T1 and CT26 cells co-cultured directly with or without ADSCs assessed by bioluminescence assay. Values are means + SEM; *, P<0.05; **, P<0.01 in unpaired t test with Welch's correction. (B) In vitro cell growth measured by cell counting of 4T1 and CT26 cells co-cultured indirectly with or without ADSCs using trans-well. Values are means + SEM; *** indicates P<0.001 using unpaired t test with Welch's correction. (C) RT-PCR of MKI67 and PCNA expression in 4T1 and CT26 cells, with GAPDH as loading control. (D) Representative bioluminescence images and (E) tumour volume measurements (mean ± SEM) of 3 × 105 4T1 cells or 1.5 × 105 CT26 cells injected subcutaneously into syngeneic mice alone with or without five folds of ADSCs. Results were taken 0, 7, 14, and 21 days after implantation; *, P<0.05 in two-way ANOVA.
Mentions: To investigate whether the cell growth of breast and colon cancer cells was influenced by ADSCs, we directly co-cultured ADSCs with 4T1 or CT26 cells. The amount of cancer cells was evaluated by in vitro bioluminescent quantification. The bioluminescence activity was strongly enhanced in cancer cells co-cultured with ADSCs compared to cancer cells alone (Figure 3A), suggesting that ADSCs could increase the number of both cancer cells. ADSCs are known as a rich source of cytokines and chemokines, which can communicate with other surrounding cells in a paracrine manner. To further determine whether ADSCs enhanced cancer cell growth via paracrine effect, we co-cultured cancer cells with ADSCs indirectly using trans-well co-culture system. Consistent with above result, ADSCs could increase the cell number of breast and colon cancer cells upon co-culture with them (Figure 3B). We further found that ADSCs could upregulate the mRNA expression of proliferation-related genes in cancer cells, including MKI67 and PCNA (Figure 3C). We then utilized syngeneic tumor models to evaluate whether the in vivo tumor growth of cancer cells were influenced by ADSCs. BALB/c mice were injected 5 × 105 4T1 or 1.5 × 105 CT26 cancer cells with ADSCs subcutaneously. The tumor growth rate was evaluated by bioluminescent imaging and volume calculation. Representative images are shown in Figure 3D, and the results of tumor volume calculation are shown in Figure 3E. These data suggest that ADSCs significantly accelerate the growth rate of breast and colon cancer cells both in cell culture and in mice.

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