Differential expression of the ccn3 (nov) proto-oncogene in human prostate cell lines and tissues

Maillard, Marjorie; Cadot, Bruno; Ball, Richard Y.; Sethia, Krishna; Edwards, Dylan R.; Perbal, Bernard; Tatoud, Roger

doi:10.1136/mp.54.4.275

Cited by 61 publications

(54 citation statements)

References 26 publications

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“…In Ewing's sarcoma, CCN3 plays a dual role, inhibiting proliferation while promoting migration and invasion of the same cells (Benini et al 2005). In comparison, melanomas overexpressing CCN3 show a higher metastatic potential studied as xenografts (Vallacchi et al 2008), while overexpression of CCN3 in human prostate cell lines (Maillard et al 2001) and high expression in high grade renal cell carcinomas (Glukhova et al 2001) favor an active role in tumorigenesis and progression.…”

Section: Ccn3 (Nov)mentioning

confidence: 99%

CCN family of proteins: critical modulators of the tumor cell microenvironment

Yeger

Perbal

2016

J. Cell Commun. Signal.

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The CCN family of proteins consisting of CCN1 (Cyr61), CCN2 (CTGF), CCN3 (NOV), CCN4 (WISP-1), CCN5 (WISP-2) and CCN6 (WISP-3) are considered matricellular proteins operating essentially in the extracellular microenvironment between cells. Evidence has also been gradually building since their first discovery of additional intracellular roles although the major activity is triggered at the cell membrane. The proteins consist of 4 motifs, a signal peptide (for secretion} followed consecutively by the IGFBP, VWC, TSP1 and CT (C-terminal cysteine knot domain) motifs, which signify their potential binding partners and functional connections to a variety of key regulators of physiological processes. With respect to cancer it is now clear that, whereas certain members can facilitate tumor behavior and progression, others can competitively counter the process. It is therefore clear that the net outcome of biological interactions in the matrix and what gets signaled or inhibited can be a function of the interplay of these CCN 1-6 proteins. Because the CCN proteins further interact with other key proteins, like growth factors in the matrix, the balance is not only important but can vary dynamically with the physiological states of tumor cells and the surrounding normal cells. The tumor niche with its many cell players has surfaced as a critical determinant of tumor behavior, invasiveness, and metastasis. It is in this context that CCN proteins should be investigated with the potential of being recognized and validated for future therapeutic approaches.

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Section: Ccn3 (Nov)mentioning

confidence: 99%

CCN family of proteins: critical modulators of the tumor cell microenvironment

Yeger

Perbal

2016

J. Cell Commun. Signal.

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“…CCN3 is aberrantly expressed in several malignancies and is associated with the progression of prostate cancer (Maillard et al, 2001), renal cell carcinoma (Glukhova et al, 2001) and Ewing's sarcoma (Manara et al, 2002), whereas in rhabdomyosarcoma and cartilage tumors, CCN3 expression correlates with tumor differentiation. Extensive studies have indicated that the biological properties of CCN3 are dependent upon the cellular context (Perbal et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of CCN3 expression as a potential mechanism for melanoma progression

et al. 2007

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Coculture of human melanocytes with keratinocytes upregulates CCN3, a matricellular protein critical to maintenance of normal homeostasis of melanocytes in the skin. CCN3 affects two fundamental features of melanocyte physiology: it inhibits melanocyte proliferation and stimulates their adhesion to the basement membrane. Here we report that expression of CCN3 is downregulated in advanced melanomas. Aggressive melanoma cell lines did not respond to treatment with CCN3 inducers, such as interleukin-1b (IL-1b), while less aggressive melanoma cell lines responded similarly to melanocytes. Immunostaining analyses revealed that CCN3 was present in melanoma cells close to the epidermal-dermal interface, but not in melanoma cells that had invaded deep into the dermis or had metastasized to lymph nodes. Contrary to our expectations, overexpression of CCN3 in 1205Lu metastatic melanoma cells did not affect their adhesion to collagen IV. However, CCN3 decreased the transcription and activation of matrix metalloproteinases and suppressed the invasion of 1205Lu melanoma cells. These results suggest that the lack of CCN3 in advanced melanoma cells contributes to their invasive phenotype. Whereas major matricellular proteins, such as osteopontin, tenascin or secreted protein acidic and rich in cysteine (SPARC), are strongly upregulated in melanoma cells; CCN3 is the first member of this family that is downregulated.

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“…CCN3 has also been linked with enhanced metastatic potential for some tumours including Ewings Sarcoma ), osteosarcoma ) and prostate neoplasia (Maillard et al 2001).…”

Section: Introductionmentioning

confidence: 99%

CCN3 suppresses mitogenic signalling and reinstates growth control mechanisms in Chronic Myeloid Leukaemia

McCallum

Lü

Price

et al. 2011

J. Cell Commun. Signal.

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CCN3, a tumour suppressor gene, is downregulated as a result of BCR-ABL tyrosine kinase activity in Chronic Myeloid Leukaemia (CML). We have established a stable CCN3 expression model in the human K562 CML cell line and have further validated the role for CCN3 in the leukaemogenic process. K562 cells stably transfected with CCN3 (K562/CCN3; 2.25×10 6 copies per 50 ng cDNA) demonstrated over 50% reduction in cell growth in comparison to cells stably transfected with empty vector (K562/control; p=0.005). K562/CCN3 cells had reduced colony formation capacity (reduced by 29.7%, p=0.03) and reduced mitogenic signalling in comparison to K562/control cells (reduced by 29.5% (p=0.002) and 37.4% (p=0.017) for phosphorylation levels of ERK and AKT respectively). K562/CCN3 cells showed an accumulation of events within the subG 0 phase of the cell cycle and increased apoptosis was confirmed by a three-fold increase in annexin V binding (p<0.05). K562/CCN3 cells exposed to Imatinib (1 μM and 5 μM) showed an increase in events within the subG 0 phase of cell cycle over 96 h and mirrored the enhanced cell kill demonstrated by Annexin staining. Wild type K562 cells treated with recombinant human Ccn3 (10 nM) in combination with Imatinib (5 μM) also displayed enhanced cell kill (p=0.008). K562/CCN3 cells displayed increased adhesion to matrigel™ (2.92±0.52 fold increase compared to K562/control) which was commensurate with increased expression of the alpha 6 and beta 4 integrins (6.53±0.47 and 1.94±0.07 fold increase in gene expression respectively (n=3, p<0.05)). CCN3 restores cellular growth regulatory properties that are absent in CML and sensitises CML cells to imatinib induced apoptosis. CCN3 may provide novel avenues for the development of alternate therapeutic strategies.

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Differential expression of the ccn3 (nov) proto-oncogene in human prostate cell lines and tissues

Abstract: (J Clin Pathol: Mol Pathol 2001;54:275-280)

Cited by 61 publications

References 26 publications

CCN family of proteins: critical modulators of the tumor cell microenvironment

CCN family of proteins: critical modulators of the tumor cell microenvironment

Downregulation of CCN3 expression as a potential mechanism for melanoma progression

CCN3 suppresses mitogenic signalling and reinstates growth control mechanisms in Chronic Myeloid Leukaemia

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