Evidence of a novel biomarker, αs1-Casein, a milk protein, in benign prostate hyperplasia

Xu, Kexin; Ma, Lulin; Wang, X; Wong, YC

doi:10.1038/sj.pcan.4500872

Cited by 14 publications

(8 citation statements)

References 26 publications

(29 reference statements)

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“…Lower levels of alpha s1 casein in normal and prostate cancer tissues, compared to benign prostate hyperplasia patients have been reported and as a result, it has been considered as a potential biomarker for diagnosis of benign prostate hyperplasia. In this study, using immunohistochemistry, the positive staining results of alpha s1 casein were as follow: zero of ten controls, 3 of 30 prostate cancer and 20 out of 22 benign prostate hyperplasia samples . Figure F shows reduced levels of lactate dehydrogenase in two of the comparisons.…”

Section: Resultsmentioning

confidence: 68%

Proteomics analysis of human breast milk to assess breast cancer risk

et al. 2018

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Detection of breast cancer (BC) in young women is challenging because mammography, the most common tool for detecting BC, is not effective on the dense breast tissue characteristic of young women. In addition to the limited means for detecting their BC, young women face a transient increased risk of pregnancy-associated BC. As a consequence, reproductively active women could benefit significantly from a tool that provides them with accurate risk assessment and early detection of BC. One potential method for detection of BC is biochemical monitoring of proteins and other molecules in bodily fluids such as serum, nipple aspirate, ductal lavage, tear, urine, saliva and breast milk. Of all these fluids, only breast milk provides access to a large volume of breast tissue, in the form of exfoliated epithelial cells, and to the local breast environment, in the form of molecules in the milk. Thus, analysis of breast milk is a non-invasive method with significant potential for assessing BC risk. Here we analyzed human breast milk by mass spectrometry (MS)-based proteomics to build a biomarker signature for early detection of BC. Ten milk samples from eight women provided five paired-groups (cancer versus control) for analysis of dysregulatedproteins: two within woman comparisons (milk from a diseased breast versus a healthy breast of the same woman) and three across women comparisons (milk from a woman with cancer versus a woman without cancer). Despite a wide range in the time between milk donation and cancer diagnosis (cancer diagnosis occurred from 1 month before to 24 months after milk donation), the levels of some proteins differed significantly between cancer and control in several of the five comparison groups. These pilot data are supportive of the idea that molecular analysis of breast milk will identify proteins informative for early detection and accurate assessment of BC risk, and warrant further research. Data are available via ProteomeXchange with identifier PXD007066.

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Section: Resultsmentioning

confidence: 68%

Proteomics analysis of human breast milk to assess breast cancer risk

et al. 2018

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“…This potentially points to a role for human CSN1S1 in connecting nutrition, innate, and adaptive immune mechanisms. Moreover, functions of human CSN1S1 may reach well beyond nutritional aspects since ectopic expression was repeatedly found in inflamed tissues such as synovial cells and cartilage of rheumatoid arthritis and osteoarthritis patients , in prostate hyperplasia and in lymph nodes of encephalomyelitic mice .…”

Section: Introductionmentioning

confidence: 99%

Human casein alpha s1 induces proinflammatory cytokine expression in monocytic cells by TLR4 signaling

Vordenbäumen

Saenger

Braukmann

et al. 2016

Molecular Nutrition Food Res

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“…The mammary gland was believed to be the sole site of expression for caseins (26), but a transgenic-mouse model showed elevated serum levels of human GM-CSF expressed under the control of the rodent as1-casein gene (27). Additionally, increased casein gene expression was found in the blood of patients with multiple sclerosis, in lymph nodes of mice with experimental encephalomyelitis in the reconvalescence phase (28), and in benign prostate hyperplasia of humans (29). These observations suggested a more widespread expression of the protein in the context of an unknown physiological function.…”

mentioning

confidence: 74%

“…The use of high concentrations of rCSN1S1 may be justified by the fact that, by this means, effects on cells can be studied more easily. Furthermore, CSN1S1 concentrations may be higher in certain tissues or microenvironments, which is suggested by the finding of increased CSN1S1 expression in prostate hyperplasia or in lymph nodes of mice suffering from encephalomyelitis (28,29). Various tissues or cells, in addition to monocytes, may contribute to the overall CSN1S1 level.…”

Section: Discussionmentioning

confidence: 99%

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Vordenbäumen

Braukmann

Petermann

et al. 2011

The Journal of Immunology

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Caseins are major constituents of mammalian milks that are thought to be exclusively expressed in mammary glands and to function primarily as a protein source, as well as to ameliorate intestinal calcium uptake. In addition, proinflammatory and immunomodulatory properties have been reported for bovine caseins. Our aim was to investigate whether human casein α s1 (CSN1S1) is expressed outside the mammary gland and possesses immunomodulatory functions in humans as well. For this purpose, CSN1S1 mRNA was detected in primary human monocytes and CD4+ and CD8+ T cells, but not in CD19+ B cells. CSN1S1 protein was traceable in supernatants of cultured primary human CD14+ monocytes by ELISA. Similarly, CSN1S1 mRNA and protein were detected in the human monocytic cell lines HL60, U937, and THP1 but not in Mono Mac 6 cells. Moreover, permeabilized human monocytes and HL60 cells could be stained by immunofluorescence, indicating intracellular expression. Recombinant human CSN1S1 was bound to the surface of Mono Mac 6 cells and upregulated the expression of GM-CSF mRNA in primary human monocytes and Mono Mac 6 cells in a time- and concentration-dependent manner. A similar increase in GM-CSF protein was found in the culture supernatants. CSN1S1-dependent upregulation of GM-CSF was specifically blocked by the addition of the p38 MAPK inhibitor ML3403. Our results indicated that human CSN1S1 may possess an immunomodulatory role beyond its nutritional function in milk. It is expressed in human monocytes and stimulates the expression of the proinflammatory cytokine GM-CSF.

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Evidence of a novel biomarker, αs1-Casein, a milk protein, in benign prostate hyperplasia

Cited by 14 publications

References 26 publications

Proteomics analysis of human breast milk to assess breast cancer risk

Proteomics analysis of human breast milk to assess breast cancer risk

Human casein alpha s1 induces proinflammatory cytokine expression in monocytic cells by TLR4 signaling

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

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