The expression of the ADAMs proteases in prostate cancer cell lines and their regulation by dihydrotestosterone

McCulloch, Daniel R.; Harvey, Mark B.; Herington, Adrian C.

doi:10.1016/s0303-7207(00)00305-1

Cited by 76 publications

(59 citation statements)

References 36 publications

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“…This result was validated by an RT -PCR analysis in PDAC cell lines, which revealed ADAM9 expression in 13 of the 20 cell lines, and by immunohistochemistry in a small set of PDACs (Grutzmann et al, 2003;Iacobuzio-Donahue et al, 2003). ADAM9 overexpression was also demonstrated in prostate, breast and liver cell carcinomas (McCulloch et al, 2000;Le Pabic et al, 2003;O'Shea et al, 2003).…”

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confidence: 57%

ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma

et al. 2004

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Gene expression profiling revealed ADAM9 to be distinctly overexpressed in pancreatic ductal adenocarcinoma (PDAC). We examined the relevance of ADAM9 expression in PDAC diagnosis and prognosis. A total of 59 infiltrating PDACs, 32 specimens from patients with chronic pancreatitis, 11 endocrine tumours and 24 acinar cell carcinomas were immunohistochemically analysed for ADAM9 expression. Staining for ADAM9 was detected in 58 out of 59 (98.3%) PDACs and in two out of 24 (8.3%) acinar cell carcinomas, but not in endocrine tumours. In the non-neoplastic pancreas, whether normal or chronically inflamed, ADAM9 was expressed in centroacinar and intralobular duct cells, but not in interlobular duct cells and their hyperplastic lesions. Pancreatic ductal adenocarcinomas showing cytoplasmic ADAM9 expression correlated with poor tumour differentiation and also with shorter overall survival than in cases showing only an apical membranous staining pattern (P ¼ 0.001). Multivariate analysis identified cytoplasmic ADAM9 expression as an independent marker of shortened survival in a set of 42 curatively (R0) resected PDAC (Po0.05, hazard ratio 2.85, 95% confidence interval: 1.21 -6.71). The results show that ADAM9 expression distinguishes PDACs from other solid pancreatic tumours. In addition, cytoplasmic ADAM9 overexpression is associated with poor differentiation and shortened survival. Therefore, ADAM9 overexpression might contribute to the aggressiveness of PDACs.

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confidence: 57%

ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma

et al. 2004

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“…This androgen-dependency could interfere with ADAM-related regulation processes since the mRNA expression of several ADAMs is regulated by androgens [126]. Indeed, ADAM-9, -10, -11, -15 and -17 are expressed in prostate cancer cells and treatment of androgen-dependent cancer cells with dihydrotestosterone leads to an upregulation of ADAM-9 and -10 mRNAs while ADAM-17 mRNA is downregulated.…”

Section: Prostate Cancermentioning

confidence: 99%

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

et al. 2008

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A disintegrin and metalloproteinases (ADAMs) are a recently discovered family of proteins that share the metalloproteinase domain with matrix metalloproteinases (MMPs). Among this family, structural features distinguish the membrane-anchored ADAMs and the secreted ADAMs with thrombospondin motifs referred to as ADAMTSs. By acting on a large panel of membrane-associated and extracellular substrates, they control several cell functions such as adhesion, fusion, migration and proliferation. The current review addresses the contribution of these proteinases in the positive and negative regulation of cancer progression as mainly mediated by the regulation of growth factor activities and integrin functions.

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“…However, reports on the expression and function of ADAM17 in prostate cancer are limited. ADAM17 mRNA expression was found in both androgen-dependent and androgen-independent prostate cancer cell lines (2). Subsequent study showed ADAM17 expression in non-cancerous (BPH) prostatic tissues was lower than that in tumor samples (20).…”

Section: Introductionmentioning

confidence: 99%

“…The growth and maintenance of cancerous cells in the early stages of prostate cancer is androgen-dependent and therapy often involves androgen deprivation (2). In the later stages therapeutic alternatives are not available, as the tumor progresses from androgen-dependence to -independence.…”

Section: Introductionmentioning

confidence: 99%

ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion

Xiao

Lin²,

Lin³

et al. 2011

Int J Oncol

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Abstract. ADAM17, also known as tumor necrosis factor-α converting enzyme (TACE), is involved in proteolytic ectodomain shedding of cell surface molecules and cytokines. Although aberrant expression of ADAM17 has been shown in various malignancies, the function of ADAM17 in prostate cancer has not been clarified. In the present study, we sought to elucidate whether ADAM17 contributes to prostate cancer cell invasion, as well as the mechanism involved in the process. The expression pattern of ADAM17 was investigated in human prostate cancer cells. The results showed that ADAM17 expression levels are correlated with the invasive ability of androgen-independent prostate cancer cell lines. Further, ADAM17 was overexpressed in cells showing high invasion characteristics, activation of the EGFR-MEK-ERK pathway, up-regulation of MMP-2, MMP-9, and an increased TGF-α release into the supernatant. However, AG1478, PD98059 and antibody against TGF-α deactivating the EGFR-MEK-ERK signaling pathway, abolished up-regulation of MMP-2, MMP-9 and prevented cell invasion. In addition, cells with knockdown of ADAM17 by siRNA exhibited low invasive ability, deactivated EGFR-MEK-ERK signaling pathway, reduced TGF-α released and down-regulation of MMP-2, MMP-9. However, these effects could be reversed by simultaneous addition of TGF-α. These data demonstrated that ADAM17 contributes to androgen-independent prostate cancer cell invasion by shedding of EGFR ligand TGF-α, which subsequently activates the EGFR-MEK-ERK signaling pathway, leading finally to overexpression of MMP-2 and MMP-9. This study suggests that the ADAM17 expression level may be a new predictive biomarker of invasion and metastasis of prostate cancer, and ADAM17 could provide a target for treating metastatic PCa. IntroductionProstate cancer (PCa) is one of the most common malignancies among Western males with an occurrence of approximately 192,280 new cases and 27,360 deaths in the US, in 2009 (1). The growth and maintenance of cancerous cells in the early stages of prostate cancer is androgen-dependent and therapy often involves androgen deprivation (2). In the later stages therapeutic alternatives are not available, as the tumor progresses from androgen-dependence to -independence. The lack of effective therapies for advanced PCa is related to a large extent to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis (3). Therefore, the identification of new predictive biomarkers, especially those that are indicative of invasiveness of the disease, which could serve as targets for establishing effectiveness of therapeutic and chemopreventive interventions, will improve clinical management of PCa (4).The ADAMs (a disintegrin and metalloproteinase) are members of the metzincin superfamily of Zn-dependent matrix metalloproteinases. They are transmembrane and secreted proteins with important roles in diverse biological functions, such as fertilization, adhesion, migration, proteolysis and signaling (5,6). Recent...

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The expression of the ADAMs proteases in prostate cancer cell lines and their regulation by dihydrotestosterone

Cited by 76 publications

References 36 publications

ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma

ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion

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