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Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells.

Walter M, Liang S, Ghosh S, Hornsby PJ, Li R - Oncogene (2009)

Bottom Line: Our study also identifies cofilin-1, a known regulator of actin dynamics, as a determinant of the tumor-promoting activity of ASCs.The cofilin-1-dependent pathway affects the production of interleukin 6 (IL-6) in ASCs.Depletion of IL-6 from the ASC-conditioned medium abrogated the stimulatory effect of ASCs on the migration and invasion of breast tumor cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.

ABSTRACT
Excessive adiposity has long been associated with increased incidence of breast cancer in post-menopausal women, and with increased mortality from breast cancer, regardless of the menopausal status. Although adipose tissue-derived estrogen contributes to obesity-associated risk for estrogen receptor (ER)-positive breast cancer, the estrogen-independent impact of adipose tissue on tumor invasion and progression needs to be elucidated. Here, we show that adipose stromal cells (ASCs) significantly stimulate migration and invasion of ER-negative breast cancer cells in vitro and tumor invasion in a co-transplant xenograft mouse model. Our study also identifies cofilin-1, a known regulator of actin dynamics, as a determinant of the tumor-promoting activity of ASCs. The cofilin-1-dependent pathway affects the production of interleukin 6 (IL-6) in ASCs. Depletion of IL-6 from the ASC-conditioned medium abrogated the stimulatory effect of ASCs on the migration and invasion of breast tumor cells. Thus, our study uncovers a link between a cytoskeleton-based pathway in ASCs and the stromal impact on breast cancer cells.

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Related in: MedlinePlus

siRNA knock-down of Cofilin-1 in ASCs reduces their migration-promoting activity(A) Cofilin-1 knocked down in ASCs by siRNA using an oligo pool and individual oligos. α-Tubulin is used as loading control. (B) Cofilin-1-knockdown ASCs were tested in the Boyden-chamber migration assay using MDA-MB-231 cells.
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Figure 3: siRNA knock-down of Cofilin-1 in ASCs reduces their migration-promoting activity(A) Cofilin-1 knocked down in ASCs by siRNA using an oligo pool and individual oligos. α-Tubulin is used as loading control. (B) Cofilin-1-knockdown ASCs were tested in the Boyden-chamber migration assay using MDA-MB-231 cells.

Mentions: To identify the potential molecular players that mediate the effect of ASCs on tumor cell migration, we used an siRNA mini-library that was used in a separate study of ASCs (Ghosh et al., manuscript submitted). The siRNA-transfected ASCs were seeded in the lower chamber of the Boyden-chamber system to assess their effects on the migration of MDA-MB-231 cells. Of all the genes targeted in the siRNA screen, cofilin-1 knockdown resulted in the greatest reduction in the ASC-mediated stimulation of tumor cell migration (Suppl. Fig, 2). To ascertain the specificity of the siRNA pool, two independent cofilin-1 siRNA oligos were tested for their effects on ASC-mediated stimulation of tumor cell migration. As shown in Fig. 3, both the siRNA pool and individual oligos were effective in reducing the cofilin-1 expression and the migration-promoting activity of ASCs. Notably, the protein levels of cofilin-1 in the knockdown cell populations correlate well with their ability to stimulate migration of MDA-MB-231 cells.


Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells.

Walter M, Liang S, Ghosh S, Hornsby PJ, Li R - Oncogene (2009)

siRNA knock-down of Cofilin-1 in ASCs reduces their migration-promoting activity(A) Cofilin-1 knocked down in ASCs by siRNA using an oligo pool and individual oligos. α-Tubulin is used as loading control. (B) Cofilin-1-knockdown ASCs were tested in the Boyden-chamber migration assay using MDA-MB-231 cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2806057&req=5

Figure 3: siRNA knock-down of Cofilin-1 in ASCs reduces their migration-promoting activity(A) Cofilin-1 knocked down in ASCs by siRNA using an oligo pool and individual oligos. α-Tubulin is used as loading control. (B) Cofilin-1-knockdown ASCs were tested in the Boyden-chamber migration assay using MDA-MB-231 cells.
Mentions: To identify the potential molecular players that mediate the effect of ASCs on tumor cell migration, we used an siRNA mini-library that was used in a separate study of ASCs (Ghosh et al., manuscript submitted). The siRNA-transfected ASCs were seeded in the lower chamber of the Boyden-chamber system to assess their effects on the migration of MDA-MB-231 cells. Of all the genes targeted in the siRNA screen, cofilin-1 knockdown resulted in the greatest reduction in the ASC-mediated stimulation of tumor cell migration (Suppl. Fig, 2). To ascertain the specificity of the siRNA pool, two independent cofilin-1 siRNA oligos were tested for their effects on ASC-mediated stimulation of tumor cell migration. As shown in Fig. 3, both the siRNA pool and individual oligos were effective in reducing the cofilin-1 expression and the migration-promoting activity of ASCs. Notably, the protein levels of cofilin-1 in the knockdown cell populations correlate well with their ability to stimulate migration of MDA-MB-231 cells.

Bottom Line: Our study also identifies cofilin-1, a known regulator of actin dynamics, as a determinant of the tumor-promoting activity of ASCs.The cofilin-1-dependent pathway affects the production of interleukin 6 (IL-6) in ASCs.Depletion of IL-6 from the ASC-conditioned medium abrogated the stimulatory effect of ASCs on the migration and invasion of breast tumor cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245, USA.

ABSTRACT
Excessive adiposity has long been associated with increased incidence of breast cancer in post-menopausal women, and with increased mortality from breast cancer, regardless of the menopausal status. Although adipose tissue-derived estrogen contributes to obesity-associated risk for estrogen receptor (ER)-positive breast cancer, the estrogen-independent impact of adipose tissue on tumor invasion and progression needs to be elucidated. Here, we show that adipose stromal cells (ASCs) significantly stimulate migration and invasion of ER-negative breast cancer cells in vitro and tumor invasion in a co-transplant xenograft mouse model. Our study also identifies cofilin-1, a known regulator of actin dynamics, as a determinant of the tumor-promoting activity of ASCs. The cofilin-1-dependent pathway affects the production of interleukin 6 (IL-6) in ASCs. Depletion of IL-6 from the ASC-conditioned medium abrogated the stimulatory effect of ASCs on the migration and invasion of breast tumor cells. Thus, our study uncovers a link between a cytoskeleton-based pathway in ASCs and the stromal impact on breast cancer cells.

Show MeSH
Related in: MedlinePlus