Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness
The tumor microenvironment harbors cancer-associated fibroblasts that function as major modulators of cancer progression. Here, we assessed to which extent distinct cancer-associated fibroblast subsets impact mammary carcinoma growth and cancer cell stemness in an orthotopic murine model. We found t...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2018-04-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2017.1414129 |
| _version_ | 1819063512440242176 |
|---|---|
| author | Maximilian Boesch Lucas Onder Hung-Wei Cheng Mario Novkovic Urs Mörbe Sieghart Sopper Guenther Gastl Wolfram Jochum Thomas Ruhstaller Michael Knauer Burkhard Ludewig |
| author_facet | Maximilian Boesch Lucas Onder Hung-Wei Cheng Mario Novkovic Urs Mörbe Sieghart Sopper Guenther Gastl Wolfram Jochum Thomas Ruhstaller Michael Knauer Burkhard Ludewig |
| author_sort | Maximilian Boesch |
| collection | DOAJ |
| description | The tumor microenvironment harbors cancer-associated fibroblasts that function as major modulators of cancer progression. Here, we assessed to which extent distinct cancer-associated fibroblast subsets impact mammary carcinoma growth and cancer cell stemness in an orthotopic murine model. We found that fibroblasts expressing the Cre recombinase under the control of the interleukin 7 promoter occupied mainly the tumor margin where they physically interacted with tumor cells. Intratumoral ablation of interleukin 7-expressing fibroblasts impaired breast tumor growth and reduced the clonogenic potential of cancer cells. Moreover, cDNA expression profiling revealed a distinct oncogenic signature of interleukin 7-producing fibroblasts. In particular, Cxcl12 expression was strongly enhanced in interleukin 7-producing fibroblasts and cell type-specific genetic ablation and systemic pharmacological inhibition revealed that the CXCL12/CXCR4 axis impacts breast tumor cell stemness. Elevated expression of CXCL12 and other stem cell factors in primary human breast cancer-associated fibroblasts indicates that certain fibroblast populations support tumor cell stemness and thereby promote breast cancer growth. |
| first_indexed | 2024-12-21T15:15:51Z |
| format | Article |
| id | doaj.art-cc35457bcd0d47768dece60b58c6014c |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-21T15:15:51Z |
| publishDate | 2018-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-cc35457bcd0d47768dece60b58c6014c2022-12-21T18:59:10ZengTaylor & Francis GroupOncoImmunology2162-402X2018-04-017410.1080/2162402X.2017.14141291414129Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemnessMaximilian Boesch0Lucas Onder1Hung-Wei Cheng2Mario Novkovic3Urs Mörbe4Sieghart Sopper5Guenther Gastl6Wolfram Jochum7Thomas Ruhstaller8Michael Knauer9Burkhard Ludewig10Institute of Immunobiology, Kantonsspital St. GallenInstitute of Immunobiology, Kantonsspital St. GallenInstitute of Immunobiology, Kantonsspital St. GallenInstitute of Immunobiology, Kantonsspital St. GallenInstitute of Immunobiology, Kantonsspital St. GallenInternal Medicine V, Medical University of InnsbruckInternal Medicine V, Medical University of InnsbruckInstitute of Pathology, Kantonsspital St. GallenBreast Center, Kantonsspital St. GallenBreast Center, Kantonsspital St. GallenInstitute of Immunobiology, Kantonsspital St. GallenThe tumor microenvironment harbors cancer-associated fibroblasts that function as major modulators of cancer progression. Here, we assessed to which extent distinct cancer-associated fibroblast subsets impact mammary carcinoma growth and cancer cell stemness in an orthotopic murine model. We found that fibroblasts expressing the Cre recombinase under the control of the interleukin 7 promoter occupied mainly the tumor margin where they physically interacted with tumor cells. Intratumoral ablation of interleukin 7-expressing fibroblasts impaired breast tumor growth and reduced the clonogenic potential of cancer cells. Moreover, cDNA expression profiling revealed a distinct oncogenic signature of interleukin 7-producing fibroblasts. In particular, Cxcl12 expression was strongly enhanced in interleukin 7-producing fibroblasts and cell type-specific genetic ablation and systemic pharmacological inhibition revealed that the CXCL12/CXCR4 axis impacts breast tumor cell stemness. Elevated expression of CXCL12 and other stem cell factors in primary human breast cancer-associated fibroblasts indicates that certain fibroblast populations support tumor cell stemness and thereby promote breast cancer growth.http://dx.doi.org/10.1080/2162402X.2017.1414129breast cancertumor microenvironmentinterleukin 7cancer-associated fibroblastcancer stem cellscxcl12 |
| spellingShingle | Maximilian Boesch Lucas Onder Hung-Wei Cheng Mario Novkovic Urs Mörbe Sieghart Sopper Guenther Gastl Wolfram Jochum Thomas Ruhstaller Michael Knauer Burkhard Ludewig Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness OncoImmunology breast cancer tumor microenvironment interleukin 7 cancer-associated fibroblast cancer stem cells cxcl12 |
| title | Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness |
| title_full | Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness |
| title_fullStr | Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness |
| title_full_unstemmed | Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness |
| title_short | Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness |
| title_sort | interleukin 7 expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness |
| topic | breast cancer tumor microenvironment interleukin 7 cancer-associated fibroblast cancer stem cells cxcl12 |
| url | http://dx.doi.org/10.1080/2162402X.2017.1414129 |
| work_keys_str_mv | AT maximilianboesch interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT lucasonder interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT hungweicheng interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT marionovkovic interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT ursmorbe interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT sieghartsopper interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT guenthergastl interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT wolframjochum interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT thomasruhstaller interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT michaelknauer interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness AT burkhardludewig interleukin7expressingfibroblastspromotebreastcancergrowththroughsustenanceoftumorcellstemness |