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Cellular Oncology
Published in: Cellular Oncology 1/2011

01-02-2011 | Original Paper

Adipose tissue derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor derived factors

Authors: Constantin Jotzu, Eckhard Alt, Gabriel Welte, Jie Li, Bryan T. Hennessy, Eswaran Devarajan, Srinivasalu Krishnappa, Severin Pinilla, Lilly Droll, Yao-Hua Song

Published in: Cellular Oncology | Issue 1/2011

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Abstract

Background

Carcinoma-associated fibroblasts (CAF) are considered to contribute to tumor growth, invasion and metastasis. However, the cell type of origin remains unknown. Since human adipose tissue derived stem cells (hASCs) are locally adjacent to breast cancer cells and might directly interact with tumor cells, we investigated whether CAFs may originate from hASCs.

Methods

hASCs cultured under different conditions were quantified for the expression of alpha smooth muscle actin. ELISA was performed using the human TGFβ1, SDF-1α and CCL5 Quantikine Kit. The invasion potential of MDAMB231 cancer cells was evaluated using a Boyden chamber with filter inserts coated with Matrigel in 24-well dishes.

Results

We demonstrated that a significant percentage of hASCs differentiated into a CAF-like myofibroblastic phenotype (e.g. expression of alpha smooth muscle actin and tenascin-C) when exposed to conditioned medium from the human breast cancer lines MDAMB231 and MCF7. The conditioned medium from MDAMB231 and MCF7 contains significant amounts of transforming growth factor-beta 1 (TGFβ1) and the differentiation of hASCs towards CAFs is dependent on TGFβ1 signaling via Smad3 in hASCs. The induction of CAFs can be abolished using a neutralizing antibody to TGFβ1 as well as by pretreatment of the hASCs with SB431542, a TGFβ1 receptor kinase inhibitor. Additionally, we found that these hASC-derived CAF-like cells exhibit functional properties of CAFs, including the ability to promote tumor cell invasion in an in vitro invasion assay, as well as increased expression of stromal-cell derived factor 1 (SDF-1) and CCL5.

Conclusion

Our data suggest that hASCs are a source of CAFs which play an important role in the tumor invasion.
Appendix
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Metadata
Title
Adipose tissue derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor derived factors
Authors
Constantin Jotzu
Eckhard Alt
Gabriel Welte
Jie Li
Bryan T. Hennessy
Eswaran Devarajan
Srinivasalu Krishnappa
Severin Pinilla
Lilly Droll
Yao-Hua Song
Publication date
01-02-2011
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 1/2011
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-011-0012-1

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