Adipose Tissue-Derived Stem Cells Differentiate into Carcinoma-Associated Fibroblast-Like Cells under the Influence of Tumor-Derived Factors
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 cel...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.3233/ACP-CLO-2010-0535 |
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| author | Constantin Jotzu Eckhard Alt Gabriel Welte Jie Li Bryan T. Hennessy Eswaran Devarajan Srinivasalu Krishnappa Severin Pinilla Lilly Droll Yao-Hua Song |
| author_facet | Constantin Jotzu Eckhard Alt Gabriel Welte Jie Li Bryan T. Hennessy Eswaran Devarajan Srinivasalu Krishnappa Severin Pinilla Lilly Droll Yao-Hua Song |
| author_sort | Constantin Jotzu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c0590896b78a40c48c42a93565475da3 |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-c0590896b78a40c48c42a93565475da32025-02-03T01:26:37ZengWileyAnalytical Cellular Pathology2210-71772210-71852010-01-01332617910.3233/ACP-CLO-2010-0535Adipose Tissue-Derived Stem Cells Differentiate into Carcinoma-Associated Fibroblast-Like Cells under the Influence of Tumor-Derived FactorsConstantin Jotzu0Eckhard Alt1Gabriel Welte2Jie Li3Bryan T. Hennessy4Eswaran Devarajan5Srinivasalu Krishnappa6Severin Pinilla7Lilly Droll8Yao-Hua Song9Department of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USADepartment of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USADepartment of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USADepartment of Systems Biology and Gynecologic Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USADepartment of Systems Biology and Gynecologic Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USADepartment of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USADepartment of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USADepartment of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USADepartment of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USADepartment of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USACarcinoma-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.http://dx.doi.org/10.3233/ACP-CLO-2010-0535 |
| spellingShingle | Constantin Jotzu Eckhard Alt Gabriel Welte Jie Li Bryan T. Hennessy Eswaran Devarajan Srinivasalu Krishnappa Severin Pinilla Lilly Droll Yao-Hua Song Adipose Tissue-Derived Stem Cells Differentiate into Carcinoma-Associated Fibroblast-Like Cells under the Influence of Tumor-Derived Factors Analytical Cellular Pathology |
| title | Adipose Tissue-Derived Stem Cells Differentiate into Carcinoma-Associated Fibroblast-Like Cells under the Influence of Tumor-Derived Factors |
| title_full | Adipose Tissue-Derived Stem Cells Differentiate into Carcinoma-Associated Fibroblast-Like Cells under the Influence of Tumor-Derived Factors |
| title_fullStr | Adipose Tissue-Derived Stem Cells Differentiate into Carcinoma-Associated Fibroblast-Like Cells under the Influence of Tumor-Derived Factors |
| title_full_unstemmed | Adipose Tissue-Derived Stem Cells Differentiate into Carcinoma-Associated Fibroblast-Like Cells under the Influence of Tumor-Derived Factors |
| title_short | Adipose Tissue-Derived Stem Cells Differentiate into Carcinoma-Associated Fibroblast-Like Cells under the Influence of Tumor-Derived Factors |
| title_sort | adipose tissue derived stem cells differentiate into carcinoma associated fibroblast like cells under the influence of tumor derived factors |
| url | http://dx.doi.org/10.3233/ACP-CLO-2010-0535 |
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