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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 | Europe PMC |
|---|---|
| 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 | 2010 |
| 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. 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. Taken together, these data suggest that hASCs are a source of CAFs which play an important role in the tumor invasion. |
| Related Links | https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC4605656&blobtype=pdf |
| ISSN | 22107177 |
| Journal | Analytical Cellular Pathology (Amsterdam) [Anal Cell Pathol (Amst)] |
| Volume Number | 33 |
| PubMed Central reference number | PMC4605656 |
| Issue Number | 2 |
| PubMed reference number | 20978328 |
| e-ISSN | 22107185 |
| DOI | 10.3233/acp-clo-2010-0535 |
| Language | English |
| Publisher | IOS Press |
| Publisher Date | 2010-01-01 |
| Access Restriction | Open |
| Rights License | Copyright © 2010 Hindawi Publishing Corporation and the authors. |
| Subject Keyword | Breast cancer mesenchymal stem cells carcinoma-associated fibroblasts transforming growth factor-beta 1 invasion |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Cancer Research Molecular Medicine Pathology and Forensic Medicine |
