Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2–CCR2 axis. The CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was reported to be associated with lung metastasis. The aim of this study was to elucidate the role of CCR2 and CCR4 in prostate cancer progression. CCR2 and CCR4 were expressed in human prostate cancer cell lines and prostate cancer tissues. In vitro co-culture of prostate cancer cells and macrophages resulted in increased CCL2 and CCR2 levels in prostate cancer cells. The addition of CCL2 induced CCL22 and CCR4 production in prostate cancer cells. The migration and invasion of prostate cancer cells via enhanced phosphorylation of Akt were promoted by CCL17 and CCL22. CCR4 may be a potential candidate for molecular-targeted therapy.

Aims To evaluate urinary incontinence using the International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF), daily pad use, and 24‐h pad weight test before and after radical prostatectomy (RP) chronologically, and the correlation between them. Methods ICIQ‐SF and questions on daily pad use provided subjective, and 24‐h pad weight test for objective evaluation. Results In total, 258 cases were recruited. The continence rate at 12 months after RP was 67% for no pad use, 87% for security 1 pad/day, and 94% for 1 pad/day. The median ICIQ‐SF total score before and at 1, 3, 6, and 12 months after RP was 0, 10, 7, 5, and 4, respectively. Incontinence patterns differed when comparing ICIQ‐SF results pre‐ and post‐RP. Significant correlation existed between the ICIQ‐SF total score, 24‐h pad weight test, and daily pad use; however, point distribution on each scatter plot varied widely. Comparing results before and at 12 months after RP revealed complete recovery for 35% of patients from the ICIQ‐SF total score, 67% from daily pad use, and 64% from the 24‐h pad weight test. A combination of all 3 showed a recovery of preoperative levels in 29% of patients. Conclusions ICIQ‐SF was effective and convenient for evaluating UI, including the pattern of UI, after RP. Significant correlation, but wide variations, among ICIQ‐SF, daily pad use, and the 24‐h pad weight test existed. The best evaluation method would be the one that can compare UI status pre‐ and post‐RP using the ICIQ‐SF and 24‐h pad weight test.

Understanding the mechanism of chemoresistance and disease progression in patients with prostate cancer is important for developing novel treatment strategies. In particular, developing resistance to cabazitaxel is a major challenge in patients with docetaxel‐resistant and castration‐resistant prostate cancer (CRPC) because cabazitaxel is often administered as a last resort. However, the mechanism by which cabazitaxel resistance develops is still unclear. C‐C motif chemokine ligands (CCL) were shown to contribute to the castration resistance of prostate cancer cells via an autocrine mechanism. Therefore, we focused on CCL as key factors of chemoresistance in prostate cancer cells. We previously established a cabazitaxel‐resistant cell line, DU145‐TxR/CxR, from a previously established paclitaxel‐resistant cell line, DU145‐TxR. cDNA microarray analysis revealed that the expression of CCL2 was upregulated in both DU145‐TxR and DU145‐TxR/CxR cells compared with DU145 cells. The secreted CCL2 protein level in DU145‐TxR and DU145‐TxR/CxR cells was also higher than in parental DU145 cells. The stimulation of DU145 cells with CCL2 increased the proliferation rate under treatments with cabazitaxel, and a CCR2 (a specific receptor of CCL2) antagonist suppressed the proliferation of DU145‐TxR and DU145‐TxR/CxR cells under treatments of cabazitaxel. The CCL2‐CCR2 axis decreased apoptosis through the inhibition of caspase‐3 and poly(ADP‐ribose) polymerase (PARP). CCL2 is apparently a key contributor to cabazitaxel resistance in prostate cancer cells. Inhibition of the CCL2‐CCR2 axis may be a potential therapeutic strategy against chemoresistant CRPC in combination with cabazitaxel.

Once castration-resistant prostate cancer (CRPC) become resistant for cabazitaxel treatment, the patients are obliged to best supportive care. Therefore, the elucidation of the mechanism of the cabazitaxel-resistance and the conquest are important themes to improve the prognosis of the patients. Then we tried to establish cabazitaxel-resistant CRPC cell lines and characterized them. We established two cabazitaxel-resistant cell lines, PC-3-TxR/CxR and DU145-TxR/CxR from PC-3-TxR and DU145-TxR cell lines previously we established. PC-3-TxR/CxR and DU145-TxR/CxR cells became resistant for cabazitaxel by 11.8-fold and 4.4-fold, respectively. The TxR/CxR cells showed cabazitaxel-resistant using SCID mice in vivo. Although expression of multi-drug resistance gene 1 (MDR1) was up-regulated in DU145-TxR compared with DU145 cells, it was not up-regulated in DU145-TxR/CxR cells any more. In contrast, expression of MDR1 gene was up-regulated in PC-3-TxR compared with PC-3 cells and it was further up-regulated in PC-3-TxR/CxR compared with PC-3-TxR cells. Comparison of cDNA microarray between PC-3-TxR and PC-3-TxR/CxR cells or between DU145-TxR and DU145-TxR/CxR cells revealed that many genes were up-regulated or down-regulated. Finally, knockdown of MDR1 recovered the sensitivity to cabazitaxel not only in PC-3-TxR/CxR cells but also DU145-TxR/CxR cells. Together, regulation of MDR1 gene is important for conquest of the cabazitaxel-resistance.

The SPL was shortest at 10 days after RP and gradually recovered thereafter in the present study. Anatomically, the glans and corpus spongiosum surrounding the urethra are an integral structure, and the proximal urethra is drawn into the pelvis during urethrovesical anastomosis. This is the first report showing that slight vertical repositioning of the membranous urethra after RP causes changes in SPL over time. These results can help inform patients about changes in penile appearance after RP.