Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells
Аутори
Piazzi, ManuelaKojić, Snežana
Capanni, Cristina
Stamenković, Nemanja
Bavelloni, Alberto
Marin, Oriano
Lattanzi, Giovanna
Blalock, William
Cenni, Vittoria
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Simple Summary Osteosarcoma is a rare malignancy of bone, primarily affecting children and young adults. The main objective of this study was to identify novel therapeutic targets to fight the progression of this insidious disease. To this aim, the role of Ankrd2, a stress- and mechano- sensor protein known for being mostly expressed in muscle fibers, was analyzed in the modulation of osteosarcoma progression. By subjecting human osteosarcoma cell lines expressing or silencing Ankrd2 to several functional assays, our results demonstrated that Ankrd2 is involved in the pathogenesis of this cancer. Nonetheless, due to observations obtained by other studies in other model systems, our findings also suggest that Ankrd2 might behave as a "double-faced" cancer driver gene. Ankrd2 is a protein known for being mainly expressed in muscle fibers, where it participates in the mechanical stress response. Since both myocytes and osteoblasts are mesenchymal-derived cells, we were interested in exami...ning the role of Ankrd2 in the progression of osteosarcoma which features a mechano-stress component. Although having been identified in many tumor-derived cell lines and -tissues, no study has yet described nor hypothesized any involvement for this protein in osteosarcoma tumorigenesis. In this paper, we report that Ankrd2 is expressed in cell lines obtained from human osteosarcoma and demonstrate a contribution by this protein in the pathogenesis of this insidious disease. Ankrd2 involvement in osteosarcoma development was evaluated in clones of Saos2, U2OS, HOS and MG63 cells stably expressing Ankrd2, through the investigation of hallmark processes of cancer cells. Interestingly, we found that exogenous expression of Ankrd2 influenced cellular growth, migration and clonogenicity in a cell line-dependent manner, whereas it was able to improve the formation of 3D spheroids in three out of four cellular models and enhanced matrix metalloproteinase (MMP) activity in all tested cell lines. Conversely, downregulation of Ankrd2 expression remarkably reduced proliferation and clonogenic potential of parental cells. As a whole, our data present Ankrd2 as a novel player in osteosarcoma development, opening up new therapeutic perspectives.
Кључне речи:
spheroids / proliferation / osteosarcoma / migration / mechanotransduction / cancer / bone / Ankrd2Извор:
Cancers, 2021, 13, 2Издавач:
- MDPI, Basel
Финансирање / пројекти:
- Associazione Italiana per la Ricerca sul Cancro [AIRC IG-2015, 17137]
- Комплексне болести као модел систем за проучавање модулације фенотипа-структурна и функционална анализа молекуларних биомаркера (RS-MESTD-Basic Research (BR or ON)-173008)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
DOI: 10.3390/cancers13020174
ISSN: 2072-6694
WoS: 000611152700001
Scopus: 2-s2.0-85099402472
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Piazzi, Manuela AU - Kojić, Snežana AU - Capanni, Cristina AU - Stamenković, Nemanja AU - Bavelloni, Alberto AU - Marin, Oriano AU - Lattanzi, Giovanna AU - Blalock, William AU - Cenni, Vittoria PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1486 AB - Simple Summary Osteosarcoma is a rare malignancy of bone, primarily affecting children and young adults. The main objective of this study was to identify novel therapeutic targets to fight the progression of this insidious disease. To this aim, the role of Ankrd2, a stress- and mechano- sensor protein known for being mostly expressed in muscle fibers, was analyzed in the modulation of osteosarcoma progression. By subjecting human osteosarcoma cell lines expressing or silencing Ankrd2 to several functional assays, our results demonstrated that Ankrd2 is involved in the pathogenesis of this cancer. Nonetheless, due to observations obtained by other studies in other model systems, our findings also suggest that Ankrd2 might behave as a "double-faced" cancer driver gene. Ankrd2 is a protein known for being mainly expressed in muscle fibers, where it participates in the mechanical stress response. Since both myocytes and osteoblasts are mesenchymal-derived cells, we were interested in examining the role of Ankrd2 in the progression of osteosarcoma which features a mechano-stress component. Although having been identified in many tumor-derived cell lines and -tissues, no study has yet described nor hypothesized any involvement for this protein in osteosarcoma tumorigenesis. In this paper, we report that Ankrd2 is expressed in cell lines obtained from human osteosarcoma and demonstrate a contribution by this protein in the pathogenesis of this insidious disease. Ankrd2 involvement in osteosarcoma development was evaluated in clones of Saos2, U2OS, HOS and MG63 cells stably expressing Ankrd2, through the investigation of hallmark processes of cancer cells. Interestingly, we found that exogenous expression of Ankrd2 influenced cellular growth, migration and clonogenicity in a cell line-dependent manner, whereas it was able to improve the formation of 3D spheroids in three out of four cellular models and enhanced matrix metalloproteinase (MMP) activity in all tested cell lines. Conversely, downregulation of Ankrd2 expression remarkably reduced proliferation and clonogenic potential of parental cells. As a whole, our data present Ankrd2 as a novel player in osteosarcoma development, opening up new therapeutic perspectives. PB - MDPI, Basel T2 - Cancers T1 - Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells IS - 2 VL - 13 DO - 10.3390/cancers13020174 ER -
@article{ author = "Piazzi, Manuela and Kojić, Snežana and Capanni, Cristina and Stamenković, Nemanja and Bavelloni, Alberto and Marin, Oriano and Lattanzi, Giovanna and Blalock, William and Cenni, Vittoria", year = "2021", abstract = "Simple Summary Osteosarcoma is a rare malignancy of bone, primarily affecting children and young adults. The main objective of this study was to identify novel therapeutic targets to fight the progression of this insidious disease. To this aim, the role of Ankrd2, a stress- and mechano- sensor protein known for being mostly expressed in muscle fibers, was analyzed in the modulation of osteosarcoma progression. By subjecting human osteosarcoma cell lines expressing or silencing Ankrd2 to several functional assays, our results demonstrated that Ankrd2 is involved in the pathogenesis of this cancer. Nonetheless, due to observations obtained by other studies in other model systems, our findings also suggest that Ankrd2 might behave as a "double-faced" cancer driver gene. Ankrd2 is a protein known for being mainly expressed in muscle fibers, where it participates in the mechanical stress response. Since both myocytes and osteoblasts are mesenchymal-derived cells, we were interested in examining the role of Ankrd2 in the progression of osteosarcoma which features a mechano-stress component. Although having been identified in many tumor-derived cell lines and -tissues, no study has yet described nor hypothesized any involvement for this protein in osteosarcoma tumorigenesis. In this paper, we report that Ankrd2 is expressed in cell lines obtained from human osteosarcoma and demonstrate a contribution by this protein in the pathogenesis of this insidious disease. Ankrd2 involvement in osteosarcoma development was evaluated in clones of Saos2, U2OS, HOS and MG63 cells stably expressing Ankrd2, through the investigation of hallmark processes of cancer cells. Interestingly, we found that exogenous expression of Ankrd2 influenced cellular growth, migration and clonogenicity in a cell line-dependent manner, whereas it was able to improve the formation of 3D spheroids in three out of four cellular models and enhanced matrix metalloproteinase (MMP) activity in all tested cell lines. Conversely, downregulation of Ankrd2 expression remarkably reduced proliferation and clonogenic potential of parental cells. As a whole, our data present Ankrd2 as a novel player in osteosarcoma development, opening up new therapeutic perspectives.", publisher = "MDPI, Basel", journal = "Cancers", title = "Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells", number = "2", volume = "13", doi = "10.3390/cancers13020174" }
Piazzi, M., Kojić, S., Capanni, C., Stamenković, N., Bavelloni, A., Marin, O., Lattanzi, G., Blalock, W.,& Cenni, V.. (2021). Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells. in Cancers MDPI, Basel., 13(2). https://doi.org/10.3390/cancers13020174
Piazzi M, Kojić S, Capanni C, Stamenković N, Bavelloni A, Marin O, Lattanzi G, Blalock W, Cenni V. Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells. in Cancers. 2021;13(2). doi:10.3390/cancers13020174 .
Piazzi, Manuela, Kojić, Snežana, Capanni, Cristina, Stamenković, Nemanja, Bavelloni, Alberto, Marin, Oriano, Lattanzi, Giovanna, Blalock, William, Cenni, Vittoria, "Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells" in Cancers, 13, no. 2 (2021), https://doi.org/10.3390/cancers13020174 . .