Identification of endothelin–1 in the pathophysiology of metastatic adenocarcinoma of the prostate

Nelson, Joel B.; Hedican, Sean P.; George, Daniel J.; Reddi, A. Hari; Piantadosi, Steven; Eisenberger, Mario A.; Simons, Jonathan W.

doi:10.1038/nm0995-944

Cited by 580 publications

(366 citation statements)

References 50 publications

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“…ET-1 null mice die shortly after birth from respiratory failure and cardiac abnormalities [30]. Also serum ET-1 levels are increased in patients with bone osteoblastic lesions [31]. ET-1 mediates its effects on bone formation through the Endothelin A (ET A ) receptor.…”

Section: Osteoblastic Bone Metastasismentioning

confidence: 99%

Mechanisms of cancer metastasis to the bone

Yin¹,

Pollock²,

Kelly³

2005

Cell Res

293

226

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Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bidirectional interactions between tumor cells and cells that make up bone result in a selective advantage for tumor growth and can lead to bone destruction or new bone matrix deposition. This review discusses our current understanding of the molecular components and mechanisms that are responsible for those interactions.

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Section: Osteoblastic Bone Metastasismentioning

confidence: 99%

Mechanisms of cancer metastasis to the bone

Yin¹,

Pollock²,

Kelly³

2005

Cell Res

293

226

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“…The specific primers for ET-1 are sense 5′-TTA AAG GGC ACT TGG GCT GA-3′, antisense 5′-AAG ATG ATT TGA CGC TGT TT-3′, representing positions 202-222/885-905 of endothelin-1 sequence (Genbank: accession S56805). The expected size of PCR products is 703 bp (Nelson et al, 1995). The primers for actin are 5′CCT CGC CTT TGC CGA TCC-3′, antisense 5′-GGA TCT TCA TGA GGT AGT CAG TC-3′.…”

Section: Rt-pcr and Northern Blot Analysismentioning

confidence: 99%

Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption

et al. 2000

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The causes for the propensity of metastasized prostate cancer cells to grow in bone and to induce osteoblastic lesions remain unresolved. Co-culture of human prostate cancer cell lines with bone slices was determined to increase the level of endothelin-1 (ET-1) mRNA and its production. ET-1 is an ejaculate protein that also stimulates osteoblasts. Osteoclastic bone resorption was significantly blocked by the presence of androgen-independent prostate cancer cells in a dose-dependent manner as that of synthetic ET-1. The inhibition could be neutralized by specific ET-1 antibody, indicating the association of prostate cancer-derived ET-1 with inhibition of bone resorption. The combined ET-1 activity on osteoclasts and osteoblasts disrupts bone remodelling. ET-1 production is also elevated in the presence of prostate-specific antigen (PSA). ET-1 in turn enhances DNA synthesis of prostate cancer cells. Interactions among cancer cells, bone, ET-1 and PSA may be critical in cancer growth and lesions in bone. © 2000 Cancer Research Campaign

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“…Additional evidence suggests that PSA may have a significant role in osteoblastic bone metastasis (Nelson et al, 1995;Shah et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression

et al. 2010

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Although the transient receptor potential melastatin 8 (TRPM8) cold receptor is highly expressed in prostate cancer (PCa) and constitutes a promising diagnostic and prognostic indicator, the natural agonists of this channel in the prostate, as well as its physiological and pathological functions, remain unknown. In this study, we identified the well-known PCa marker, prostatespecific antigen (PSA), as a physiological TRPM8 agonist. Electrophysiological and Ca 2 þ imaging studies demonstrated that PSA activated TRPM8-mediated current by the bradykinin 2 receptor signaling pathway. Further investigation of this mechanism by cell-surface biotinylation revealed that the increase in TRPM8 current induced by PSA was due to an increase in the number of functional TRPM8 channels on the plasma membrane. Importantly, wound-healing and migration assays revealed that TRPM8 activation by PSA reduced motility of the PC3 PCa cell line, suggesting that plasma membrane TRPM8 has a protective role in PCa progression. Consequently, PSA was identified as a natural TRPM8 agonist in the prostate and we propose a putative physiological role for both of these proteins in carcinogenesis, making this pathway a potentially important target for anticancer agent development.

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Identification of endothelin–1 in the pathophysiology of metastatic adenocarcinoma of the prostate

Cited by 580 publications

References 50 publications

Mechanisms of cancer metastasis to the bone

Mechanisms of cancer metastasis to the bone

Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption

PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression

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