Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer
Abstract Background Cancer-associated fibroblasts (CAFs) have been shown to support tumor development in a variety of cancers. Different markers were applied to classify CAFs in order to elucidate their impact on tumor progression. However, the exact mechanism by which CAFs enhance cancer developmen...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Cellular & Molecular Biology Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11658-022-00351-7 |
| _version_ | 1828803913145384960 |
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| author | Anna Muchlińska Anna Nagel Marta Popęda Jolanta Szade Magdalena Niemira Jacek Zieliński Jarosław Skokowski Natalia Bednarz-Knoll Anna J. Żaczek |
| author_facet | Anna Muchlińska Anna Nagel Marta Popęda Jolanta Szade Magdalena Niemira Jacek Zieliński Jarosław Skokowski Natalia Bednarz-Knoll Anna J. Żaczek |
| author_sort | Anna Muchlińska |
| collection | DOAJ |
| description | Abstract Background Cancer-associated fibroblasts (CAFs) have been shown to support tumor development in a variety of cancers. Different markers were applied to classify CAFs in order to elucidate their impact on tumor progression. However, the exact mechanism by which CAFs enhance cancer development and metastasis is yet unknown. Methods Alpha-smooth muscle actin (α-SMA) was examined immunohistochemically in intratumoral CAFs of nonmetastatic breast cancers and correlated with clinicopathological data. Four CAF cell lines were isolated from patients with luminal breast cancer (lumBC) and classified according to the presence of α-SMA protein. Conditioned medium (CM) from CAF cultures was used to assess the influence of CAFs on lumBC cell lines: MCF7 and T47D cells using Matrigel 3D culture assay. To identify potential factors accounting for promotion of tumor growth by α-SMAhigh CAFs, nCounter PanCancer Immune Profiling Panel (NanoString) was used. Results In luminal breast cancer, presence of intratumoral CAFs expressing high level of α-SMA (13% of lumBC group) correlated with poor prognosis (p = 0.019). In in vitro conditions, conditioned medium obtained from primary cultures of α-SMA-positive CAFs isolated from luminal tumors was observed to enhance growth of lumBC cell line colonies in 3D Matrigel, in contrast to CM derived from α-SMA-negative CAFs. Multigene expression analysis indicated that osteopontin (OPN) was overexpressed in α-SMA-positive CAFs in both clinical samples and in vitro models. OPN expression was associated with higher percentage of Ki67-positive cells in clinical material (p = 0.012), while OPN blocking in α-SMA-positive CAF-derived CM attenuated growth of lumBC cell line colonies in 3D Matrigel. Conclusions Our findings demonstrate that α-SMA-positive CAFs might enhance tumor growth via secretion of OPN. |
| first_indexed | 2024-12-12T07:32:01Z |
| format | Article |
| id | doaj.art-bcb21bbd65f547e9be0b1b35a9ebb28c |
| institution | Directory Open Access Journal |
| issn | 1425-8153 1689-1392 |
| language | English |
| last_indexed | 2024-12-12T07:32:01Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj.art-bcb21bbd65f547e9be0b1b35a9ebb28c2022-12-22T00:33:00ZengBMCCellular & Molecular Biology Letters1425-81531689-13922022-06-0127111410.1186/s11658-022-00351-7Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancerAnna Muchlińska0Anna Nagel1Marta Popęda2Jolanta Szade3Magdalena Niemira4Jacek Zieliński5Jarosław Skokowski6Natalia Bednarz-Knoll7Anna J. Żaczek8Laboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, Medical University of GdanskLaboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, Medical University of GdanskLaboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, Medical University of GdanskDepartment of Pathomorphology, Medical University of GdanskClinical Research Centre, Medical University of BialystokDepartment of Surgical Oncology, Medical University of GdanskDepartment of Surgical Oncology, Medical University of GdanskLaboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, Medical University of GdanskLaboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, Medical University of GdanskAbstract Background Cancer-associated fibroblasts (CAFs) have been shown to support tumor development in a variety of cancers. Different markers were applied to classify CAFs in order to elucidate their impact on tumor progression. However, the exact mechanism by which CAFs enhance cancer development and metastasis is yet unknown. Methods Alpha-smooth muscle actin (α-SMA) was examined immunohistochemically in intratumoral CAFs of nonmetastatic breast cancers and correlated with clinicopathological data. Four CAF cell lines were isolated from patients with luminal breast cancer (lumBC) and classified according to the presence of α-SMA protein. Conditioned medium (CM) from CAF cultures was used to assess the influence of CAFs on lumBC cell lines: MCF7 and T47D cells using Matrigel 3D culture assay. To identify potential factors accounting for promotion of tumor growth by α-SMAhigh CAFs, nCounter PanCancer Immune Profiling Panel (NanoString) was used. Results In luminal breast cancer, presence of intratumoral CAFs expressing high level of α-SMA (13% of lumBC group) correlated with poor prognosis (p = 0.019). In in vitro conditions, conditioned medium obtained from primary cultures of α-SMA-positive CAFs isolated from luminal tumors was observed to enhance growth of lumBC cell line colonies in 3D Matrigel, in contrast to CM derived from α-SMA-negative CAFs. Multigene expression analysis indicated that osteopontin (OPN) was overexpressed in α-SMA-positive CAFs in both clinical samples and in vitro models. OPN expression was associated with higher percentage of Ki67-positive cells in clinical material (p = 0.012), while OPN blocking in α-SMA-positive CAF-derived CM attenuated growth of lumBC cell line colonies in 3D Matrigel. Conclusions Our findings demonstrate that α-SMA-positive CAFs might enhance tumor growth via secretion of OPN.https://doi.org/10.1186/s11658-022-00351-7Cancer-associated fibroblastLuminal breast cancerAlpha-smooth muscle actinOsteopontin |
| spellingShingle | Anna Muchlińska Anna Nagel Marta Popęda Jolanta Szade Magdalena Niemira Jacek Zieliński Jarosław Skokowski Natalia Bednarz-Knoll Anna J. Żaczek Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer Cellular & Molecular Biology Letters Cancer-associated fibroblast Luminal breast cancer Alpha-smooth muscle actin Osteopontin |
| title | Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer |
| title_full | Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer |
| title_fullStr | Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer |
| title_full_unstemmed | Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer |
| title_short | Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer |
| title_sort | alpha smooth muscle actin positive cancer associated fibroblasts secreting osteopontin promote growth of luminal breast cancer |
| topic | Cancer-associated fibroblast Luminal breast cancer Alpha-smooth muscle actin Osteopontin |
| url | https://doi.org/10.1186/s11658-022-00351-7 |
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