Biomarkers for prostate cancer

Leman, Eddy S.; Getzenberg, Robert H.

doi:10.1002/jcb.22227

Cited by 64 publications

(31 citation statements)

References 47 publications

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“…Monitoring of PSA is generally recommended in men over 50 years old to screen for prostate cancer; however, there is significant controversy with respect to its use as a marker for the appearance of the disease (1)(2)(3)(4)(5)(6). By contrast, substantial data support its use in monitoring progression and metastasis (1,2,5). Recently, a Phase II controlled trial suggested that immunization against PSA prolongs patient survival, suggesting a direct role for PSA in the pathobiology of the disease (7).…”

Section: Prostate-specific Antigen (Psa)mentioning

confidence: 99%

Ligation of Prostate Cancer Cell Surface GRP78 Activates a Proproliferative and Antiapoptotic Feedback Loop

Misra

Payne

Pizzo

2011

Journal of Biological Chemistry

113

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GRP78, a well characterized chaperone in the endoplasmic reticulum, is critical to the unfolded protein response. More recently, it has been identified on the cell surface, where it has many roles. On cancer cells, it functions as a signaling receptor coupled to proproliferative/antiapoptotic and promigratory mechanisms. In the current study, we demonstrate that ligation of prostate cancer cell surface GRP78 by its natural ligand, activated ␣ 2 -macroglobulin (␣ 2 M*), results in a 2-3-fold upregulation in the synthesis of prostate-specific antigen (PSA). The PSA is secreted into the medium as an active proteinase, where it binds to native ␣ 2 M. The resultant ␣ 2 M⅐PSA complexes bind to GRP78, causing a 1.5-2-fold increase in the activation of MEK1/2, ERK1/2, S6K, and Akt, which is coupled with a 2-3-fold increase in DNA and protein synthesis. PSA is a marker for the progression of prostate cancer, but its mechanistic role in the disease is unclear. The present studies suggest that PSA may be involved in a signal transduction-dependent feedback loop, whereby it promotes a more aggressive behavior by human prostate cancer cells.Prostate-specific antigen (PSA) 2 is a serine proteinase that complexes with serum proteinase inhibitors, including ␣ 2 -macroglobulin (␣ 2 M) (1). Monitoring of PSA is generally recommended in men over 50 years old to screen for prostate cancer; however, there is significant controversy with respect to its use as a marker for the appearance of the disease (1-6). By contrast, substantial data support its use in monitoring progression and metastasis (1, 2, 5). Recently, a Phase II controlled trial suggested that immunization against PSA prolongs patient survival, suggesting a direct role for PSA in the pathobiology of the disease (7). Studies have shown that PSA produced by metastatic prostate cancer cells is involved in bone remodeling, a common feature in the bony metastasis of this disease (8). There is, however, little other evidence indicating a direct role for PSA in disease progression. ␣ 2 M is synthesized by many tissues, particularly the liver; however, it is also produced locally in prostate stromal tissue, where it is available to complex with PSA (9). When a proteinase attacks the so-called "bait region," thiol esters in each of the four ␣ 2 M subunits rupture, and the protein undergoes a very large conformational change, exposing receptor recognition sites in each subunit (10). Two receptors have been identified for activated forms of ␣ 2 M (␣ 2 M*), namely the LDL receptor-related protein (LRP) and cell surface-associated GRP78 (glucose-regulated protein of M r ϳ78,000) (10, 11). In addition to proteinases, exposure of ␣ 2 M to small primary amines or ammonia, by direct attack on the thiol esters, produces ␣ 2 M* (10). Although GRP78 is primarily known as a resident endoplasmic reticulum chaperone, it appears on the cell surface of many types of malignant cells, including human prostate cancer (12-16). Here it has many functions, including serving as an ␣ 2 M* signaling re...

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Section: Prostate-specific Antigen (Psa)mentioning

confidence: 99%

Ligation of Prostate Cancer Cell Surface GRP78 Activates a Proproliferative and Antiapoptotic Feedback Loop

Misra

Payne

Pizzo

2011

Journal of Biological Chemistry

113

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“…To overcome the PSA limitations, a series of new biomolecules, including cellular and genetic biomarkers, such as PCA3 [4], AMACR [5], specific metalloproteinases [6] and glycan profiles [7], are proposed for PCa screening [8]. Simultaneously, a search for a more sensitive, accurate and reliable biomolecule objectively measureable in accessible fluids, such as serum, is pursued, together with the development of a robust, easy-to-use, clinical test, based on novel biomarkers that could improve not only the diagnosis but also prognosis and management of this cancer.…”

Section: Introductionmentioning

confidence: 99%

A PSA-guided approach for a better diagnosis of prostatic adenocarcinoma based on MALDI profiling and peptide identification

Fania¹,

Sogno²,

Vasso³

et al. 2015

Clinica Chimica Acta

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“…Yes, the clinical method for screening EPCa is prostate specific antigen (PSA) test. 2 But unfortunately, PSA test has been found to be unreliable in practice. Both the false negative rate (15.2%) and false positive rate (30%) are very high, though it is the most widely used clinical method for EPCa.…”

mentioning

confidence: 99%

Nano Pt@ZIF8 Modified Electrode and Its Application to Detect Sarcosine

Yang

Wang

Yang

et al. 2018

J. Electrochem. Soc.

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Sarcosine is a newly discovered effective biomarker for prostate cancer. However, the low concentration of sarcosine in tissue cells, plasma or urine blocks the development of sarcosine biosensors. In this manuscript, porous zeolitic imidazolate framework-8 (ZIF8) was synthesized and was used as carriers to load nano platinum (Pt@ZIF8). The porous structure of ZIF8 helped to stabilize the nano platinum and keep its high catalytic activity. The Pt@ZIF8 modified sarcosine biosensor had good response toward sarcosine due to its unique structure and morphology. The linear range of the as prepared biosensor is from 5 to 30 μM, which is consistent with the detection demand. The prepared sarcosine biosensor is suitable to be developed as a kind of portable diagnostic facilities for prostate cancer. Prostate cancer (PCa) is one of the major diseases that influence the health and life expectancy of men over 50 years' old.

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Biomarkers for prostate cancer

Cited by 64 publications

References 47 publications

Ligation of Prostate Cancer Cell Surface GRP78 Activates a Proproliferative and Antiapoptotic Feedback Loop

Ligation of Prostate Cancer Cell Surface GRP78 Activates a Proproliferative and Antiapoptotic Feedback Loop

A PSA-guided approach for a better diagnosis of prostatic adenocarcinoma based on MALDI profiling and peptide identification

Nano Pt@ZIF8 Modified Electrode and Its Application to Detect Sarcosine

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