High expression of connective tissue growth factor accelerates dissemination of leukaemia
To improve treatment of acute lymphoblastic leukaemia (ALL), a better understanding of disease development is needed to tailor new therapies. Connective tissue growth factor (CTGF/CCN2) is highly expressed in leukaemia cells from the majority of paediatric patients with B-lineage ALL (pre-B ALL). CT...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
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Nature Publishing Group
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/59373 |
| _version_ | 1848760462425980928 |
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| author | Wells, J. Howlett, M. Halse, H. Heng, J. Ford, J. Cheung, Laurence Samuels, A. Crook, M. Charles, A. Cole, C. Kees, U. |
| author_facet | Wells, J. Howlett, M. Halse, H. Heng, J. Ford, J. Cheung, Laurence Samuels, A. Crook, M. Charles, A. Cole, C. Kees, U. |
| author_sort | Wells, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | To improve treatment of acute lymphoblastic leukaemia (ALL), a better understanding of disease development is needed to tailor new therapies. Connective tissue growth factor (CTGF/CCN2) is highly expressed in leukaemia cells from the majority of paediatric patients with B-lineage ALL (pre-B ALL). CTGF is a matricellular protein and plays a role in aggressive cancers. Here we have genetically engineered leukaemia cells to modulate CTGF expression levels. Elevated CTGF levels accelerated disease dissemination and reduced survival in NOD/SCID mice. In vitro studies showed that CTGF protein induces stromal cell proliferation, promotes adhesion of leukaemia cells to stromal cells and leads to overexpression of genes associated with cell cycle and synthesis of extracellular matrix (ECM). Corresponding data from our leukaemia xenograft models demonstrated that CTGF leads to increased proliferation of non-leukaemia cells and deposition of ECM in the bone marrow. We document for the first time a functional role of CTGF in altering disease progression in a lymphoid malignancy. The findings provide support for targeting the bone marrow microenvironment in aggressive forms of leukaemia. |
| first_indexed | 2025-11-14T10:16:10Z |
| format | Journal Article |
| id | curtin-20.500.11937-59373 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:16:10Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-593732018-02-13T02:11:19Z High expression of connective tissue growth factor accelerates dissemination of leukaemia Wells, J. Howlett, M. Halse, H. Heng, J. Ford, J. Cheung, Laurence Samuels, A. Crook, M. Charles, A. Cole, C. Kees, U. To improve treatment of acute lymphoblastic leukaemia (ALL), a better understanding of disease development is needed to tailor new therapies. Connective tissue growth factor (CTGF/CCN2) is highly expressed in leukaemia cells from the majority of paediatric patients with B-lineage ALL (pre-B ALL). CTGF is a matricellular protein and plays a role in aggressive cancers. Here we have genetically engineered leukaemia cells to modulate CTGF expression levels. Elevated CTGF levels accelerated disease dissemination and reduced survival in NOD/SCID mice. In vitro studies showed that CTGF protein induces stromal cell proliferation, promotes adhesion of leukaemia cells to stromal cells and leads to overexpression of genes associated with cell cycle and synthesis of extracellular matrix (ECM). Corresponding data from our leukaemia xenograft models demonstrated that CTGF leads to increased proliferation of non-leukaemia cells and deposition of ECM in the bone marrow. We document for the first time a functional role of CTGF in altering disease progression in a lymphoid malignancy. The findings provide support for targeting the bone marrow microenvironment in aggressive forms of leukaemia. 2016 Journal Article http://hdl.handle.net/20.500.11937/59373 10.1038/onc.2015.525 Nature Publishing Group restricted |
| spellingShingle | Wells, J. Howlett, M. Halse, H. Heng, J. Ford, J. Cheung, Laurence Samuels, A. Crook, M. Charles, A. Cole, C. Kees, U. High expression of connective tissue growth factor accelerates dissemination of leukaemia |
| title | High expression of connective tissue growth factor accelerates dissemination of leukaemia |
| title_full | High expression of connective tissue growth factor accelerates dissemination of leukaemia |
| title_fullStr | High expression of connective tissue growth factor accelerates dissemination of leukaemia |
| title_full_unstemmed | High expression of connective tissue growth factor accelerates dissemination of leukaemia |
| title_short | High expression of connective tissue growth factor accelerates dissemination of leukaemia |
| title_sort | high expression of connective tissue growth factor accelerates dissemination of leukaemia |
| url | http://hdl.handle.net/20.500.11937/59373 |