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

Leguit, Roos J.; Raymakers, Reinier; Hebeda, Konnie M.; Goldschmeding, Roel

doi:10.1007/s12079-020-00602-2

Cited by 16 publications

(15 citation statements)

References 361 publications

(723 reference statements)

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“…Jia et al also proved CCN4-induced type I collagen linearization facilitates tumor cell invasion and promotes spontaneous breast cancer metastasis, without significantly affecting gene expression (Jia et al, 2019). CCN2 and its fragments also have been implicated in the regulation of a multitude of biological phenomena in cancers, which was not only associated with fibrosis, but also with mesenchymal stem cells (Leguit et al, 2021). Different CCN proteins also enhance or suppress each other's action in the TME (Peidl et al, 2019).…”

Section: Ccn Proteins Acting As Critical Modulators Of the Tmementioning

confidence: 99%

CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment

Jia

Zhang

et al. 2021

Front. Genet.

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The crosstalk between tumor cells and the tumor microenvironment (TME), triggers a variety of critical signaling pathways and promotes the malignant progression of cancer. The success rate of cancer therapy through targeting single molecule of this crosstalk may be extremely low, whereas co-targeting multiple components could be complicated design and likely to have more side effects. The six members of cellular communication network (CCN) family proteins are scaffolding proteins that may govern the TME, and several studies have shown targeted therapy of CCN family proteins may be effective for the treatment of cancer. CCN protein family shares similar structures, and they mutually reinforce and neutralize each other to serve various roles that are tightly regulated in a spatiotemporal manner by the TME. Here, we review the current knowledge on the structures and roles of CCN proteins in different types of cancer. We also analyze CCN mRNA expression, and reasons for its diverse relationship to prognosis in different cancers. In this review, we conclude that the discrepant functions of CCN proteins in different types of cancer are attributed to diverse TME and CCN truncated isoforms, and speculate that targeting CCN proteins to rebalance the TME could be a potent anti-cancer strategy.

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Section: Ccn Proteins Acting As Critical Modulators Of the Tmementioning

confidence: 99%

CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment

Jia

Zhang

et al. 2021

Front. Genet.

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“…How CCN2 may mediate invasion, metastasis and drug resistance in K562-ADM cells waits to be determined. More recently Leguit et al (2021) presented a highly comprehensive review of the role of CCN2 in bone marrow and malignant hematopoiesis.…”

Section: Ccn2mentioning

confidence: 99%

“…How CCN2 may mediate invasion, metastasis and drug resistance in K562‐ADM cells waits to be determined. More recently Leguit et al (2021) presented a highly comprehensive review of the role of CCN2 in bone marrow and malignant hematopoiesis. They present a complex picture of the many interactions of CCN2 with multiple other proteins, binding to a large number of different cell surface receptors and the triggering of several prominent signaling pathways.…”

Section: Lymphoma and Leukemiasmentioning

confidence: 99%

The CCN axis in cancer development and progression

Yeger

Perbal²

2021

J. Cell Commun. Signal.

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Since the authors first reviewed this subject in 2016 significant progress has been documented in the CCN field with advances made in the understanding of how members of the CCN family of proteins, CCN1‐6, contribute to the pathogenesis and progression, positive and negative, of a larger variety of cancers. As termed matricellular proteins, and more recently the connective communication network, it has become clearer that members of the CCN family interact complexly with other proteins in the extracellular microenvironment, membrane signaling proteins, and can also operate intracellularly at the transcriptional level. In this review we expand on this earlier information providing new detailed information and insights that appropriate a much greater involvement and importance of their role in multiple aspects of cancer. Despite all the new information many more questions have been raised and intriguing results generated that warrant greater investigation. In order to permit the reader to smoothly integrate the new information we discuss all relevant CCN members in the context of cancer subtypes. We have harmonized the nomenclature with CCN numbering for easier comparisons. Finally, we summarize what new has been learned and provide a perspective on how our knowledge about CCN1‐6 is being used to drive new initiatives on cancer therapeutics.

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“…Rather than just preserving structural stability, the primary role of CCN members is to promote cell-extracellular matrix contact. By combining with heparan sulphate, and proteoglycan, CCNs play vital roles in a variety of processes in the biological systems (27,28) .…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood mRNA and Protein Levels of CCN1 and CCN3 in Psoriatic Arthritis: A Case-Control Study

Esawy¹,

Kotb²,

Baioumy³

et al. 2023

The Egyptian Journal of Hospital Medicine

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Background: Patients with psoriasis may develop psoriatic arthritis (PsA), an inflammatory joint disorder. Measuring cellular communication network (CCN) expression levels can help in disease diagnosis and prognosis. The purpose of this study was to assess the diagnostic value of CCN1 and CCN3 expressions for PsA. Patients and methods: Thirty-seven PsA patients, 37 psoriasis patients, and 37 matched healthy controls participated in a case-control study. ELISA was used to detect protein levels while qRT-PCR was used to evaluate gene expression. Results: Patients with PsA and psoriasis had greater serum and expression levels of CCN1 compared to controls (p< 0.0001). Patients with PsA and psoriasis had greater serum and expression levels of CCN1 compared to controls (p= 0.003, p< 0.0001). Both CCN3 levels in PsA patients were greater than in controls (p< 0.0001), but patients with psoriasis did not significantly differ from controls (p=0.13, p=0.38). When compared to psoriasis patients, PsA patients had greater serum and expression levels of CCN3 (p< 0.0001). In terms of psoriasis duration and severity, CCN1 exhibited a positive relation. It was shown that CCN3 and both the duration and severity of arthritis correlated positively. All markers were positively correlated with inflammatory markers. Conclusions: The most accurate marker for PsA detection was CCN3 expression, followed by the serum level of CCN1. However, CCN1 expression was the most accurate marker for the differentiation between psoriasis and PsA, followed by CCN3 expression. CCN3 could be a marker for PsA severity. These preliminary data need further studies to confirm their findings.

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

Cited by 16 publications

References 361 publications

CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment

CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment

The CCN axis in cancer development and progression

Peripheral Blood mRNA and Protein Levels of CCN1 and CCN3 in Psoriatic Arthritis: A Case-Control Study

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