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Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis.

Yin SY, Jian FY, Chen YH, Chien SC, Hsieh MC, Hsiao PW, Lee WH, Kuo YH, Yang NS - Nat Commun (2016)

Bottom Line: Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression.Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel.Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities.

View Article: PubMed Central - PubMed

Affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.

ABSTRACT
Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression. Here we investigate the role of IL-25, an endogenous anticancer factor secreted from TAFs, in suppression of mouse 4T1 mammary tumour metastasis. We show that a synthetic dihydrobenzofuran lignan (Q2-3), the dimerization product of plant caffeic acid methyl ester, suppresses 4T1 metastasis by increasing fibroblastic IL-25 activity. The secretion of IL-25 from treated human or mouse fibroblasts is enhanced in vitro, and this activity confers a strong suppressive effect on growth activity of test carcinoma cells. Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel. Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities.

No MeSH data available.


Related in: MedlinePlus

In vivo treatment of Q2-3 confers comparable anti-metastatic activity with IL-25 administration.(a) Tumour-resected mice (n=8 per group) were treated with PBS (0.1% DMSO in saline), IL-25 (200 ng per mice), Q2-3 (100 μg kg−1) or co-treated with IL-25 and Q2-3 for 3 weeks. Quantification of tumour metastasis by measuring luciferase activity in photons s−1 cm−2 sr−1 in mice revealed along the indicated time course. (b) Survival of test mice after different treatments. NS, no significant difference between the Q2-3 and co-treatment groups (Kaplan–Meier results were analysed by log-rank test). Similar results were obtained from three independent experiments.
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f6: In vivo treatment of Q2-3 confers comparable anti-metastatic activity with IL-25 administration.(a) Tumour-resected mice (n=8 per group) were treated with PBS (0.1% DMSO in saline), IL-25 (200 ng per mice), Q2-3 (100 μg kg−1) or co-treated with IL-25 and Q2-3 for 3 weeks. Quantification of tumour metastasis by measuring luciferase activity in photons s−1 cm−2 sr−1 in mice revealed along the indicated time course. (b) Survival of test mice after different treatments. NS, no significant difference between the Q2-3 and co-treatment groups (Kaplan–Meier results were analysed by log-rank test). Similar results were obtained from three independent experiments.

Mentions: In this study, the effect of IL-25 treatment in vivo was also compared for its additive versus overlapping effect. The co-treatment of mice with Q2-3 (100 μg kg−1) and IL-25 (10 μg kg−1) was found to confer a similar, rather than additive effect on anti-metastatic activity, as detected in a Q2-3 treatment only mouse group (Fig. 6a). Consistently, the mice in the co-treatment group also showed a survival rate increased by a similar level to the Q2-3-treated group, as compared with the mice in the untreated group (Fig. 6b). In other words, the anti-metastatic effect of Q2-3 in vivo can be effectively substituted by the administration of exogenous IL-25. These results also support the critical role of IL-25 in the anti-metastatic effect of Q2-3.


Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis.

Yin SY, Jian FY, Chen YH, Chien SC, Hsieh MC, Hsiao PW, Lee WH, Kuo YH, Yang NS - Nat Commun (2016)

In vivo treatment of Q2-3 confers comparable anti-metastatic activity with IL-25 administration.(a) Tumour-resected mice (n=8 per group) were treated with PBS (0.1% DMSO in saline), IL-25 (200 ng per mice), Q2-3 (100 μg kg−1) or co-treated with IL-25 and Q2-3 for 3 weeks. Quantification of tumour metastasis by measuring luciferase activity in photons s−1 cm−2 sr−1 in mice revealed along the indicated time course. (b) Survival of test mice after different treatments. NS, no significant difference between the Q2-3 and co-treatment groups (Kaplan–Meier results were analysed by log-rank test). Similar results were obtained from three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837478&req=5

f6: In vivo treatment of Q2-3 confers comparable anti-metastatic activity with IL-25 administration.(a) Tumour-resected mice (n=8 per group) were treated with PBS (0.1% DMSO in saline), IL-25 (200 ng per mice), Q2-3 (100 μg kg−1) or co-treated with IL-25 and Q2-3 for 3 weeks. Quantification of tumour metastasis by measuring luciferase activity in photons s−1 cm−2 sr−1 in mice revealed along the indicated time course. (b) Survival of test mice after different treatments. NS, no significant difference between the Q2-3 and co-treatment groups (Kaplan–Meier results were analysed by log-rank test). Similar results were obtained from three independent experiments.
Mentions: In this study, the effect of IL-25 treatment in vivo was also compared for its additive versus overlapping effect. The co-treatment of mice with Q2-3 (100 μg kg−1) and IL-25 (10 μg kg−1) was found to confer a similar, rather than additive effect on anti-metastatic activity, as detected in a Q2-3 treatment only mouse group (Fig. 6a). Consistently, the mice in the co-treatment group also showed a survival rate increased by a similar level to the Q2-3-treated group, as compared with the mice in the untreated group (Fig. 6b). In other words, the anti-metastatic effect of Q2-3 in vivo can be effectively substituted by the administration of exogenous IL-25. These results also support the critical role of IL-25 in the anti-metastatic effect of Q2-3.

Bottom Line: Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression.Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel.Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities.

View Article: PubMed Central - PubMed

Affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.

ABSTRACT
Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression. Here we investigate the role of IL-25, an endogenous anticancer factor secreted from TAFs, in suppression of mouse 4T1 mammary tumour metastasis. We show that a synthetic dihydrobenzofuran lignan (Q2-3), the dimerization product of plant caffeic acid methyl ester, suppresses 4T1 metastasis by increasing fibroblastic IL-25 activity. The secretion of IL-25 from treated human or mouse fibroblasts is enhanced in vitro, and this activity confers a strong suppressive effect on growth activity of test carcinoma cells. Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel. Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities.

No MeSH data available.


Related in: MedlinePlus