Although accumulating preclinical evidence indicates the involvement of androgen receptor signals in bladder cancer (BC) development, its clinical relevance remains unclear. We aimed to evaluate the predictive role of androgen deprivation therapy (ADT) in BC recurrence in prostate cancer (PC) patients.We retrospectively reviewed 20,328 patients with PC diagnosed during 1991–2013 and identified 239 (1.2%) men having primary BC. After excluding ineligible patients, 162 patients made up a final cohort.With a median follow-up of 62 months, 38 (50%) of 76 control patients without ADT experienced BC recurrence, while 19 (22%) of 86 did in ADT group. Thus, patients having received ADT for their PC showed a significantly lower risk of BC recurrence (5-year actuarial recurrence-free survival: 76% v 40%; P < 0.001) and also had a significantly smaller number of recurrence episodes (5-year cumulative recurrence: 0.44 v 1.54; P < 0.001), compared to the control patients. A multivariable analysis revealed ADT as an independent prognosticator (hazard ratio, 0.29; 95% confidence interval, 0.17–0.49) for BC recurrence.This is the first clinical study showing that ADT significantly reduces the risk of BC recurrence.

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Ovarian cancer has one of the poorest prognoses among carcinomas. Advanced ovarian cancer often develops ascites and peritoneal dissemination, which is one of the poor prognostic factors. From the perspective of the “seed and soil” hypothesis, the intra-abdominal environment is like the soil for the growth of ovarian cancer (OvCa) and mesothelial cells (MCs) line the top layer of this soil. In recent years, various functions of MCs have been reported, including supporting cancer in the OvCa microenvironment. We refer to OvCa-associated MCs (OCAMs) as MCs that are stimulated by OvCa and contribute to its progression. OCAMs promote OvCa cell adhesion to the peritoneum, invasion, and metastasis. Elucidation of these functions may lead to the identification of novel therapeutic targets that can delay OvCa progression, which is difficult to cure.

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Adipocyte-rich omentum offers "good soil" for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and protumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro coculturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon coculturing with O-ADF. Additionally, exogenous transforming growth factor-β1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/β-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks.