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Cited by 236

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

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

Open access
Jotzu, Constantin, Alt, Eckhard, Welte, Gabriel, Li, Jie, Hennessy, Bryan T., Devarajan, Eswaran, Krishnappa, Srinivasalu, Pinilla, Severin, Droll, Lilly, Song, Yao-Hua·2011·Cellular Oncology

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.

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Metadata

Authors
Jotzu, C., Alt, E., Welte, G., Li, J., Hennessy, B. T., Devarajan, E., Krishnappa, S., Pinilla, S., Droll, L., & Song, Y.-H.
Venue
Cellular Oncology
Published
2011-02
Volume
34
Issue
1
Pages
55-67
ISSN
  • 2211-3428
  • 1875-8606
OpenAlex
W2115883010
Cited by
236
References
10
FWCI
4.70
Type
journal article
Language
en
Open access
green

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Jotzu, C., Alt, E., Welte, G., Li, J., Hennessy, B. T., Devarajan, E., Krishnappa, S., Pinilla, S., Droll, L., & Song, Y.-H. (2011). Adipose tissue derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor derived factors. Cellular Oncology. https://doi.org/10.1007/s13402-011-0012-1

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