nm23 protein expression in fine-needle aspirates from breast carcinoma

Sauer, Torill; Furu, Irene; Beraki, Kahsai; Jebsen, Peter; Ormerod, Eli; Næss, Oddvar

doi:10.1002/(sici)1097-0142(19980425)84:2<109::aid-cncr7>3.0.co;2-k

Cited by 20 publications

(4 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nm23 genes have been proposed as metastasis suppressor genes based on clinical studies, which exhibited a correlation between development of metastatic disease and reduced NDPK protein and/or mRNA levels in many but not all cancers (for review, see Backer and Hamby, 1998). However, the role of these genes as metastasis suppressors is controversal since in more recent clinicial studies an association between metastatic potential and nm23 protein levels has not been found in patients with melanoma (Easty et al , 1996; van den Oord et al , 1997) and conflicting results have been obtained in studies of patients with breast carcinoma (Heimann et al ., 1998; Sauer et al , 1997; Russell et al ., 1997; Sawan et al ., 1997). Several factors complicate the interpretation of correlation studies.…”

mentioning

confidence: 99%

Expression of a catalytically inactive H118Y mutant of nm23-H2 suppresses the metastatic potential of line IV Cl 1 human melanoma cells

et al. 2000

View full text Add to dashboard Cite

Nm23‐H1 and nm23‐H2 are putative metastasis suppressor genes that encode nucleoside diphosphate kinase (NDPK) A and B. NDPKs form oligomers distributed between soluble and particulate fractions of cells and therefore may exert their effects as either soluble or bound proteins. To determine whether metastasis‐related functions of NDPKs are mediated by their catalytic activity in membrane bound or soluble complexes, we have stably transfected highly metastatic human melanoma Line IV Cl 1 cells with wild‐type and catalytically inactive (H118Y) nm23‐H1 and nm23‐H2 genes and assayed their metastatic potential in nude mice. Transfection with wild‐type nm23‐H1 and nm23‐H2 genes and catalytically inactive nm23‐H1 did not significantly (all p > 0.10) alter the metastatic potential of Line IV Cl 1 cells while transfection with catalytically inactive nm23‐H2 significantly (p < 0.01) reduced their metastatic potential. The lack of effect of transfection with wild‐type and catalytically inactive nm23‐H1 suggests that neither soluble nor membrane bound NDPK A affect the metastatic potential of Line IV Cl 1 cells. The metastasis suppressive effect of catalytically inactive NDPK B overexpression suggests that competition with bound complexes containing catalytically active NDPK B inhibits metastasis of Line IV Cl 1 cells. These results imply that bound NDPK B promotes metastasis and suggest that inhibition of its function or of its binding to critical sites may be a useful approach to limit the development of metastases in human melanoma. Int. J. Cancer 88:547–553, 2000. © 2000 Wiley‐Liss, Inc.

show abstract

mentioning

confidence: 99%

Expression of a catalytically inactive H118Y mutant of nm23-H2 suppresses the metastatic potential of line IV Cl 1 human melanoma cells

et al. 2000

View full text Add to dashboard Cite

show abstract

“…NM23 was originally described as non-metastatic gene 23, which was found in mouse carcinoma cells and was thought to be inversely related to metastasis (Postel, 2003; Palmieri et al , 2006) although this has been controversial. There is evidence to support an intracellular role for NM23/NDPK in tumour metastasis (Hamby et al , 2000; Roymans et al , 2002), and high tissue levels of NDPK-A protein have been found in patients with breast carcinoma (Heimann et al , 1998; Sauer et al , 1998). Nucleoside diphosphate kinases are secreted by various solid and haematological malignancies (Anzinger et al , 2001; Niitsu et al , 2001; Okabe-Kado et al , 2005a) and promote growth of acute myelogenous leukaemia cells (Okabe-Kado et al , 2009b) and endothelial cells in vitro (Rumjahn et al , 2007).…”

mentioning

confidence: 99%

A role for nucleotides in support of breast cancer angiogenesis: heterologous receptor signalling

et al. 2011

View full text Add to dashboard Cite

Background:Human breast carcinoma cells secrete an adenosine 5′-diphosphate transphosphorylase (sNDPK) known to induce endothelial cell tubulogenesis in a P2Y receptor-dependent manner. We examined sNDPK secretion and its effects on human endothelial cells.Methods:Nucleoside diphosphate kinase (NDPK) secretion was measured by western blot and enzyme-linked immunosorbent assay, while transphosphorylase activity was measured using the luciferin-luciferase ATP assay. Activation of MAPK was determined by western blot analysis, immunofluorescence and endothelial cell proliferation and migration.Results:A panel of breast cancer cell lines with origin as ductal carcinoma, adenocarcinoma or medullary carcinoma, secrete sNDPK-A/B. Addition of purified NDPK-B to endothelial cultures activated VEGFR-2 and Erk1/2, both of which were blocked by inhibitors of NDPK and P2Y receptors. Activation of VEGFR-2 and ErK1/2 by 2-methylthio-ATP (2MeS-ATP) was blocked by pretreatment with the P2Y1-specific antagonist MRS2179, the proto-oncogene non-receptor tyrosine kinase (Src) inhibitor PP2 or the VEGFR-2 antagonist SU1498. Nucleoside diphosphate kinase-B stimulates cell growth and migration in a concentration-dependent manner comparable to the effect of vascular endothelial growth factor. Treatment of endothelial cells with either NDPK-B or 2MeS-ATP induced migration, blocked by P2Y1, Src or VEGFR-2 antagonists.Conclusion:sNDPK supports angiogenesis. Understanding the mechanism of action of sNDPK and P2Y1 nucleotide signalling in metastasis and angiogenesis represent new therapeutic targets for anti-angiogenic therapies to benefit patients.

show abstract

“…The hypothesis that there is a role for a shed or secreted form of NM23/NDPK subserving breast cancer development has suffered from the NM23 dogma of Steeg [66] and others if the staunch criticism we have received is any measure. Nonetheless, it is clear from in vitro [61,67,68] and recent in vivo work from our lab [69] together with published work from others [34,45-47] that secreted NM23 contributes to our understanding of metastatic potential.…”

Section: Discussionmentioning

confidence: 99%

Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum

Buxton

Yokdang

2011

Cancers

View full text Add to dashboard Cite

The notion that breast cancers can survive in an individual patient in a dormant state only to grow as metastatic disease in the future, is in our view incontrovertibly established. Convincing too is the evidence that surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. Accepting that many deaths due to breast cancer might be averted were we to understand the cellular mechanisms underlying escape from dormancy, we have examined the extracellular signals produced by breast cancers derived from women with metastatic breast disease. In this perspective, we explore the role of extracellular nucleotide signaling that we have proposed constitutes a pathological axis from the transformed tumor cell to the endothelium in the service of intravasation, dissemination, extravasation and angiogenesis. A role for the dinucleotide kinase NM23/NDPK (nucleoside diphosphate kinase) secreted by breast tumor cells in the generation of signals that stimulate vascular leakiness, anti-thrombosis, endothelial migration and growth, constitutes a mechanistic basis for escape from latency and offers putative therapeutic targets for breast cancer management not previously appreciated.

show abstract

nm23 protein expression in fine-needle aspirates from breast carcinoma

Cited by 20 publications

References 31 publications

Expression of a catalytically inactive H118Y mutant of nm23-H2 suppresses the metastatic potential of line IV Cl 1 human melanoma cells

Expression of a catalytically inactive H118Y mutant of nm23-H2 suppresses the metastatic potential of line IV Cl 1 human melanoma cells

A role for nucleotides in support of breast cancer angiogenesis: heterologous receptor signalling

Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum

Contact Info

Product

Resources

About