Novel CT domain-encoding splice forms of CTGF/CCN2 are expressed in B-lineage acute lymphoblastic leukaemia

Welch, Mat; Howlett, Meegan; Halse, Heloise M.; Greene, Wayne K.; Kees, Ursula R.

doi:10.1016/j.leukres.2015.05.008

Cited by 5 publications

(9 citation statements)

References 58 publications

(66 reference statements)

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“…The CTGF gene (6q23.2) is a relatively short gene composed of 5 exons that code for a 349-amino acid protein. A novel splice variant of CTGF encoding the C-terminal domain has been identified in the pediatric precursor B cell acute lymphoblastic l e u k e m i a w h i c h m a y b e i n v o l v e d w i t h tumorigenesis [5].…”

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confidence: 99%

Connective tissue growth factor (CTGF) from basics to clinics

et al. 2018

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Connective tissue growth factor, also known as CCN2, is a cysteine-rich matricellular protein involved in the control of biological processes, such as cell proliferation, differentiation, adhesion and angiogenesis, as well as multiple pathologies, such as tumor development and tissue fibrosis. Here, we describe the molecular and biological characteristics of CTGF, its regulation and various functions in the spectrum of development and regeneration to fibrosis. We further outline the preclinical and clinical studies concerning compounds targeting CTGF in various pathologies with the focus on heart, lung, liver, kidney and solid organ transplantation. Finally, we address the advances and pitfalls of translational fibrosis research and provide suggestions to move towards a better management of fibrosis.

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confidence: 99%

Connective tissue growth factor (CTGF) from basics to clinics

et al. 2018

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“…The N-terminal domain (modules I and II) has been shown to mediate differentiation and collagen synthesis, and the C-terminal domain (modules III and IV) has been shown to regulate cell proliferation (Gao and Brigstock 2004 ; Hall-Glenn and Lyons 2011 ). A recently study showed that C-terminal domain of CTGF was associated with cell proliferation in leukaemia (Welch et al 2015 ). It has been reported that the C-terminal domain of CTGF could stimulate cellular adhesion via the αv-β3 receptor (Ball et al 2003 ; Hoshijima et al 2006 ) and was involved in the fibrosis process (Rodrigues-Diez et al 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Bioscreening and expression of a camel anti-CTGF VHH nanobody and its renaturation by a novel dialysis–dilution method

Xue

Fan

et al. 2016

AMB Expr

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The variable regions of the camel heavy chain antibody, also known as nanobody is the smallest antibody with antigen-binding efficiency. CTGF is considered important during extracellular matrix deposition which was involved in the pathogenesis of fibrosis related diseases. There are several anti-CTGF-C nanobody drugs under developing in pharmacy. In this study, we described the screening of a novel anti-CTGF-C nanobody from the peripheral blood of immunized camel by phage display. The screened nanobody was further expressed and purified from E. coli cells. A sophisticated dialysis–dilution method was designed for the in vitro refolding of the nanobody. The results showed that the expressed nanobody was consisted of 135 amino acid and mainly expressed as inclusion body in E. coli cells. The dialysis–dilution method was very effective and the recovery rate of the renaturation was more than 80 %. The ELISA result suggested the nanobody had been well refolded showing a superior CTGF binding activity to the commercial mouse anti-CTGF-C mAb. In conclusion, the anti-CTGF-C nonobody had been successfully screened by phage display. The dialysis–dilution refolding method was very effective and the recovery rate reached over 80 %.Electronic supplementary materialThe online version of this article (doi:10.1186/s13568-016-0249-1) contains supplementary material, which is available to authorized users.

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“…CCN2 is mainly secreted as an extracellular protein and has been identified in various human biological fluids (Bradham et al 1991;Yang et al 1998). Loss of its 2 kDa N-terminal secretory signal peptide leads to intracellular retention of the protein (Welch et al 2015).…”

Section: Ccn2 Proteinmentioning

confidence: 99%

“…B‐ALL cells can also secrete CCN2 (Boag et al 2007; Welch et al 2015; Wells et al 2016), and addition of rhCCN2 promotes adhesion of B‐ALL cells to stromal cells in vitro, which induces them to overexpress genes associated with cell cycle, intracellular transport and ECM synthesis (Wells et al 2016). Therefore, CCN2 secreted by B‐ALL cells might also enhance leukemia engraftment due to its modifying effects on the microenvironment and ECM interactions (Wells et al 2016).…”

Section: Ccn2 and Malignant Hematopoiesismentioning

confidence: 99%

“…Alternative splicing of CCN2 in B‐ALL is described by one study, which showed several novel short CCN2 mRNA isoforms (alternative splice forms) in B‐ALL cell lines and B‐ALL specimens (Welch et al 2015). The splice forms all exhibited variable loss of sequences corresponding to exons 1–3, and in some cases loss of exon 4, but always full retention of exon 5 containing the CT domain (Welch et al 2015).…”

Section: Ccn2 and Malignant Hematopoiesismentioning

confidence: 99%

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CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment, normal and malignant hematopoiesis

Leguit

Raymakers²,

Hebeda

et al. 2021

J. Cell Commun. Signal.

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CCN2, formerly termed Connective Tissue Growth Factor, is a protein belonging to the Cellular Communication Network (CCN)-family of secreted extracellular matrix-associated proteins. As a matricellular protein it is mainly considered to be active as a modifier of signaling activity of several different signaling pathways and as an orchestrator of their cross-talk. Furthermore, CCN2 and its fragments have been implicated in the regulation of a multitude of biological processes, including cell proliferation, differentiation, adhesion, migration, cell survival, apoptosis and the production of extracellular matrix products, as well as in more complex processes such as embryonic development, angiogenesis, chondrogenesis, osteogenesis, fibrosis, mechanotransduction and inflammation. Its function is complex and context dependent, depending on cell type, state of differentiation and microenvironmental context. CCN2 plays a role in many diseases, especially those associated with fibrosis, but has also been implicated in many different forms of cancer. In the bone marrow (BM), CCN2 is highly expressed in mesenchymal stem/stromal cells (MSCs). CCN2 is important for MSC function, supporting its proliferation, migration and differentiation. In addition, stromal CCN2 supports the maintenance and longtime survival of hematopoietic stem cells, and in the presence of interleukin 7, stimulates the differentiation of pro-B lymphocytes into pre-B lymphocytes. Overexpression of CCN2 is seen in the majority of B-acute lymphoblastic leukemias, especially in certain cytogenetic subgroups associated with poor outcome. In acute myeloid leukemia, CCN2 expression is increased in MSCs, which has been associated with leukemic engraftment in vivo. In this review, the complex function of CCN2 in the BM microenvironment and in normal as well as malignant hematopoiesis is discussed. In addition, an overview is given of data on the remaining CCN family members regarding normal and malignant hematopoiesis, having many similarities and some differences in their function.

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Novel CT domain-encoding splice forms of CTGF/CCN2 are expressed in B-lineage acute lymphoblastic leukaemia

Cited by 5 publications

References 58 publications

Connective tissue growth factor (CTGF) from basics to clinics

Connective tissue growth factor (CTGF) from basics to clinics

Bioscreening and expression of a camel anti-CTGF VHH nanobody and its renaturation by a novel dialysis–dilution method

CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment, normal and malignant hematopoiesis

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