title: Stromal response to prostate cancer: nanotechnology-based detection of thioredoxin-interacting protein partners distinguishes prostate cancer associated stroma from that of benign prostatic hyperplasia.
abstract: Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in prostate cancer, however, molecular markers of the stromal response to prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal biomarkers detected with a thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with Hematoxylin & Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using antibodies to thioredoxin reductase 1, thioredoxin reductase 2 or peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (p = 0.0127) than that of benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied thioredoxin interacting protein partners mirrored the fluorescence pattern seen with the nanodevice. However, thioredoxin reductase 2 protein was clearly shown to be a biomarker of prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with benign prostatic hyperplasia from that associated with prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with antibodies used in this study, originates from multiple thioredoxin interacting protein partners that distinguish the M2 neutrophil and macrophage associated inflammatory response in prostate cancer-associated stroma from the CD4+ T-Lymphocyte linked inflammation in benign prostatic hyperplasia.
authors.affiliation: City of Hope, Duarte, California, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Singer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Linehan
authors.forename: Gail
authors.initials: G
authors.lastname: Babilonia
authors.forename: S Ashraf
authors.initials: SA
authors.lastname: Imam
authors.forename: David
authors.initials: D
authors.lastname: Smith
authors.forename: Sofia
authors.initials: S
authors.lastname: Loera
authors.forename: Timothy
authors.initials: T
authors.lastname: Wilson
authors.forename: Steven
authors.initials: S
authors.lastname: Smith
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015925:Cryopreservation; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D036103:Nanotechnology / Q000379:methods*; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D013194:Staining and Labeling; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D054481:Thioredoxin Reductase 1 / Q000235:genetics* / Q000378:metabolism; D054482:Thioredoxin Reductase 2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; C516124:TXNRD1 protein, human; C516127:TXNRD2 protein, human; D054481:Thioredoxin Reductase 1; D054482:Thioredoxin Reductase 2