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

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

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

Content Provider	Springer Nature Link
Author	Jotzu, Constantin Alt, Eckhard Welte, Gabriel Li, Jie Hennessy, Bryan T. Devarajan, Eswaran Krishnappa, Srinivasalu Pinilla, Severin Droll, Lilly Song, Yao Hua
Copyright Year	2011
Abstract	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.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.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.Our data suggest that hASCs are a source of CAFs which play an important role in the tumor invasion.
Starting Page	55
Ending Page	67
Page Count	13
File Format	PDF
ISSN	22113428
Journal	Cellular Oncology
Volume Number	34
Issue Number	1
e-ISSN	18758606
Language	English
Publisher	Springer Netherlands
Publisher Date	2011-02-15
Publisher Institution	International Society for Cellular Oncology
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Breast cancer Mesenchymal stem cells Carcinoma-associated fibroblasts Transforming growth factor-beta 1 Invasion Cancer Research Biomedicine general Pathology Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Molecular Medicine Oncology

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