Patterns of specific genomic alterations associated with poor prognosis in high-grade renal cell carcinomas

Glukhova, Liubov; Angevin, Eric; Lavialle, Christian; Cadot, Bruno; Terrier‐Lacombe, Marie‐José; Perbal, Bernard; Bernheim, Alain; Goguel, A

doi:10.1016/s0165-4608(01)00477-0

Cited by 44 publications

(36 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Ccn3 (Nov)mentioning

confidence: 99%

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

Yeger

Perbal

2016

J. Cell Commun. Signal.

Self Cite

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…The functions of CCN3 protein among these different tissues might, however, be very different. Although CCN3 was originally described as antiproliferative (Joliot et al, 1992;Scholz et al, 1996) and its expression was associated with differentiation and growth arrest in Wilm's tumour, chondrosarcomas and rhabdomyosarcomas (Chevalier et al, 1998;Manara et al, 2002;Yu et al, 2003), more recent data correlate CCN3 with increased proliferative index of 3T3 fibroblast and tissue samples of prostate and renal carcinomas (Liu et al, 1999;Glukhova et al, 2001;Maillard et al, 2001). In osteosarcoma, it is inversely associated with expression of liver/bone/kidney alkaline phosphatase isoform (Manara et al, 2002), an early marker of osteoblastic differentiation (Stein et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

In Ewing's sarcoma CCN3(NOV) inhibits proliferation while promoting migration and invasion of the same cell type

et al. 2005

Self Cite

View full text Add to dashboard Cite

Altered expression of CCN3 has been observed in a variety of musculoskeletal tumours, including Ewing's sarcoma (ES). Despite its widespread distribution, very little is known about its biological functions and molecular mechanisms of action. We transfected CCN3 gene into a CCN3-negative ES cell line and analysed the in vitro and in vivo behaviours of stably transfected clones. Forced expression of CCN3 significantly reduced cell proliferation in vitro, growth in anchorage-independent conditions, and tumorigenicity in nude mice. Despite the antiproliferative effect, CCN3-transfected ES cells displayed increased migration and invasion of Matrigel. The decreased expression of a2b1 integrin receptor and the increased amount of cell surface-associated matrix metalloproteinase (MMP)-9 following the expression of CCN3 may be the basis for the increased migratory abilities of transfected cells. Cells lacking a 2 b 1 are less facilitated to have stable anchorage since the predominant collagen extracted from ES tissue is indeed type I collagen, and proMMP-9 was recently found to provide a cellular switch between stationary and migratory ES cell phase. Our findings are in line with those recently obtained in glioblastoma. However, the underlying molecular mechanisms appear to be different, further highlighting the importance of the cellular context in the regulation of function of CCN proteins.

show abstract

Patterns of specific genomic alterations associated with poor prognosis in high-grade renal cell carcinomas

Cited by 44 publications

References 24 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

In Ewing's sarcoma CCN3(NOV) inhibits proliferation while promoting migration and invasion of the same cell type

Contact Info

Product

Resources

About