Fibroblasts Influence Survival and Therapeutic Response in a 3D Co-Culture Model.
In recent years, evidence has indicated that the tumor microenvironment (TME) plays a significant role in tumor progression. Fibroblasts represent an abundant cell population in the TME and produce several growth factors and cytokines. Fibroblasts generate a suitable niche for tumor cell survival an...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4460080?pdf=render |
| _version_ | 1819045913330450432 |
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| author | Meher Majety Leon P Pradel Manuela Gies Carola H Ries |
| author_facet | Meher Majety Leon P Pradel Manuela Gies Carola H Ries |
| author_sort | Meher Majety |
| collection | DOAJ |
| description | In recent years, evidence has indicated that the tumor microenvironment (TME) plays a significant role in tumor progression. Fibroblasts represent an abundant cell population in the TME and produce several growth factors and cytokines. Fibroblasts generate a suitable niche for tumor cell survival and metastasis under the influence of interactions between fibroblasts and tumor cells. Investigating these interactions requires suitable experimental systems to understand the cross-talk involved. Most in vitro experimental systems use 2D cell culture and trans-well assays to study these interactions even though these paradigms poorly represent the tumor, in which direct cell-cell contacts in 3D spaces naturally occur. Investigating these interactions in vivo is of limited value due to problems regarding the challenges caused by the species-specificity of many molecules. Thus, it is essential to use in vitro models in which human fibroblasts are co-cultured with tumor cells to understand their interactions. Here, we developed a 3D co-culture model that enables direct cell-cell contacts between pancreatic, breast and or lung tumor cells and human fibroblasts/ or tumor-associated fibroblasts (TAFs). We found that co-culturing with fibroblasts/TAFs increases the proliferation in of several types of cancer cells. We also observed that co-culture induces differential expression of soluble factors in a cancer type-specific manner. Treatment with blocking antibodies against selected factors or their receptors resulted in the inhibition of cancer cell proliferation in the co-cultures. Using our co-culture model, we further revealed that TAFs can influence the response to therapeutic agents in vitro. We suggest that this model can be reliably used as a tool to investigate the interactions between a tumor and the TME. |
| first_indexed | 2024-12-21T10:36:07Z |
| format | Article |
| id | doaj.art-6aaa1c2fac1f47e5b9556be98f7a7cac |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T10:36:07Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6aaa1c2fac1f47e5b9556be98f7a7cac2022-12-21T19:07:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e012794810.1371/journal.pone.0127948Fibroblasts Influence Survival and Therapeutic Response in a 3D Co-Culture Model.Meher MajetyLeon P PradelManuela GiesCarola H RiesIn recent years, evidence has indicated that the tumor microenvironment (TME) plays a significant role in tumor progression. Fibroblasts represent an abundant cell population in the TME and produce several growth factors and cytokines. Fibroblasts generate a suitable niche for tumor cell survival and metastasis under the influence of interactions between fibroblasts and tumor cells. Investigating these interactions requires suitable experimental systems to understand the cross-talk involved. Most in vitro experimental systems use 2D cell culture and trans-well assays to study these interactions even though these paradigms poorly represent the tumor, in which direct cell-cell contacts in 3D spaces naturally occur. Investigating these interactions in vivo is of limited value due to problems regarding the challenges caused by the species-specificity of many molecules. Thus, it is essential to use in vitro models in which human fibroblasts are co-cultured with tumor cells to understand their interactions. Here, we developed a 3D co-culture model that enables direct cell-cell contacts between pancreatic, breast and or lung tumor cells and human fibroblasts/ or tumor-associated fibroblasts (TAFs). We found that co-culturing with fibroblasts/TAFs increases the proliferation in of several types of cancer cells. We also observed that co-culture induces differential expression of soluble factors in a cancer type-specific manner. Treatment with blocking antibodies against selected factors or their receptors resulted in the inhibition of cancer cell proliferation in the co-cultures. Using our co-culture model, we further revealed that TAFs can influence the response to therapeutic agents in vitro. We suggest that this model can be reliably used as a tool to investigate the interactions between a tumor and the TME.http://europepmc.org/articles/PMC4460080?pdf=render |
| spellingShingle | Meher Majety Leon P Pradel Manuela Gies Carola H Ries Fibroblasts Influence Survival and Therapeutic Response in a 3D Co-Culture Model. PLoS ONE |
| title | Fibroblasts Influence Survival and Therapeutic Response in a 3D Co-Culture Model. |
| title_full | Fibroblasts Influence Survival and Therapeutic Response in a 3D Co-Culture Model. |
| title_fullStr | Fibroblasts Influence Survival and Therapeutic Response in a 3D Co-Culture Model. |
| title_full_unstemmed | Fibroblasts Influence Survival and Therapeutic Response in a 3D Co-Culture Model. |
| title_short | Fibroblasts Influence Survival and Therapeutic Response in a 3D Co-Culture Model. |
| title_sort | fibroblasts influence survival and therapeutic response in a 3d co culture model |
| url | http://europepmc.org/articles/PMC4460080?pdf=render |
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