Cancers, Vol. 14, Pages 6020: TNF Signaling Is Required for Castration-Induced Vascular Damage Preceding Prostate Cancer Regression

Cancers, Vol. 14, Pages 6020: TNF Signaling Is Required for Castration-Induced Vascular Damage Preceding Prostate Cancer Regression Cancers doi: 10.3390/cancers14246020 Authors: John J. Krolewski Shalini Singh Kai Sha Neha Jaiswal Steven G. Turowski Chunliu Pan Laurie J. Rich Mukund Seshadri Kent L. Nastiuk The mainstay treatment for locally advanced, recurrent, or metastatic prostate cancer (PrCa) is androgen deprivation therapy (ADT). ADT causes prostate cancers to shrink in volume, or regress, by inducing epithelial tumor cell apoptosis. In normal, non-neoplastic murine prostate, androgen deprivation via castration induces prostate gland regression that is dependent on TNF signaling. In addition to this direct mechanism of action, castration has also been implicated in an indirect mechanism of prostate epithelial cell death, which has been described as vascular regression. The initiating event is endothelial cell apoptosis and/or increased vascular permeability. This subsequently leads to reduced blood flow and perfusion, and then hypoxia, which may enhance epithelial cell apoptosis. Castration-induced vascular regression has been observed in both normal and neoplastic prostates. We used photoacoustic, power Doppler, and contrast-enhanced ultrasound imaging, and CD31 immunohistochemical staining of the microvasculature to assess vascular integrity in the period immediately following castration, enabling us to test the role of TNF signaling in vascul...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research