Silencing of CD44 gene expression in human 143-B osteosarcoma cells promotes metastasis of intratibial tumors in SCID mice.
Osteosarcoma (OS) is the most frequent primary malignant bone cancer in children and adolescents with a high propensity for lung metastasis. Therefore, it is of great importance to identify molecular markers leading to increased metastatic potential in order to devise more effective therapeutic stra...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3614951?pdf=render |
| _version_ | 1811325040021471232 |
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| author | Ana Gvozdenovic Matthias J E Arlt Carmen Campanile Patrick Brennecke Knut Husmann Walter Born Roman Muff Bruno Fuchs |
| author_facet | Ana Gvozdenovic Matthias J E Arlt Carmen Campanile Patrick Brennecke Knut Husmann Walter Born Roman Muff Bruno Fuchs |
| author_sort | Ana Gvozdenovic |
| collection | DOAJ |
| description | Osteosarcoma (OS) is the most frequent primary malignant bone cancer in children and adolescents with a high propensity for lung metastasis. Therefore, it is of great importance to identify molecular markers leading to increased metastatic potential in order to devise more effective therapeutic strategies that suppress metastasis, the major cause of death in OS. CD44, the principal receptor for the extracellular matrix component hyaluronan (HA), is frequently found overexpressed in tumor cells and has been implicated in metastatic spread in various cancer types. Here, we investigated the effects of stable shRNA-mediated silencing of CD44 gene products on in vitro and in vivo metastatic properties of the highly metastatic human 143-B OS cell line. In vitro, CD44 knockdown resulted in a 73% decrease in the adhesion to HA, a 57% decrease in the migration rate in a trans-filter migration assay, and a 28% decrease in the cells' capacity for anchorage-independent growth in soft agar compared to the control cells, implicating that CD44 expression contributes to the metastatic activity of 143-B cells. However, making use of an orthotopic xenograft OS mouse model, we demonstrated that reduced CD44 expression facilitated primary tumor growth and formation of pulmonary metastases. The enhanced malignant phenotype was associated with decreased adhesion to HA and reduced expression of the tumor suppressor merlin in vivo. In conclusion, our study identified CD44 as a metastasis suppressor in this particular experimental OS model. |
| first_indexed | 2024-04-13T14:24:54Z |
| format | Article |
| id | doaj.art-2d1642759ffe43d095769fde8eab1d58 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T14:24:54Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2d1642759ffe43d095769fde8eab1d582022-12-22T02:43:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6032910.1371/journal.pone.0060329Silencing of CD44 gene expression in human 143-B osteosarcoma cells promotes metastasis of intratibial tumors in SCID mice.Ana GvozdenovicMatthias J E ArltCarmen CampanilePatrick BrenneckeKnut HusmannWalter BornRoman MuffBruno FuchsOsteosarcoma (OS) is the most frequent primary malignant bone cancer in children and adolescents with a high propensity for lung metastasis. Therefore, it is of great importance to identify molecular markers leading to increased metastatic potential in order to devise more effective therapeutic strategies that suppress metastasis, the major cause of death in OS. CD44, the principal receptor for the extracellular matrix component hyaluronan (HA), is frequently found overexpressed in tumor cells and has been implicated in metastatic spread in various cancer types. Here, we investigated the effects of stable shRNA-mediated silencing of CD44 gene products on in vitro and in vivo metastatic properties of the highly metastatic human 143-B OS cell line. In vitro, CD44 knockdown resulted in a 73% decrease in the adhesion to HA, a 57% decrease in the migration rate in a trans-filter migration assay, and a 28% decrease in the cells' capacity for anchorage-independent growth in soft agar compared to the control cells, implicating that CD44 expression contributes to the metastatic activity of 143-B cells. However, making use of an orthotopic xenograft OS mouse model, we demonstrated that reduced CD44 expression facilitated primary tumor growth and formation of pulmonary metastases. The enhanced malignant phenotype was associated with decreased adhesion to HA and reduced expression of the tumor suppressor merlin in vivo. In conclusion, our study identified CD44 as a metastasis suppressor in this particular experimental OS model.http://europepmc.org/articles/PMC3614951?pdf=render |
| spellingShingle | Ana Gvozdenovic Matthias J E Arlt Carmen Campanile Patrick Brennecke Knut Husmann Walter Born Roman Muff Bruno Fuchs Silencing of CD44 gene expression in human 143-B osteosarcoma cells promotes metastasis of intratibial tumors in SCID mice. PLoS ONE |
| title | Silencing of CD44 gene expression in human 143-B osteosarcoma cells promotes metastasis of intratibial tumors in SCID mice. |
| title_full | Silencing of CD44 gene expression in human 143-B osteosarcoma cells promotes metastasis of intratibial tumors in SCID mice. |
| title_fullStr | Silencing of CD44 gene expression in human 143-B osteosarcoma cells promotes metastasis of intratibial tumors in SCID mice. |
| title_full_unstemmed | Silencing of CD44 gene expression in human 143-B osteosarcoma cells promotes metastasis of intratibial tumors in SCID mice. |
| title_short | Silencing of CD44 gene expression in human 143-B osteosarcoma cells promotes metastasis of intratibial tumors in SCID mice. |
| title_sort | silencing of cd44 gene expression in human 143 b osteosarcoma cells promotes metastasis of intratibial tumors in scid mice |
| url | http://europepmc.org/articles/PMC3614951?pdf=render |
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