Immunohistochemical expression of PDGFR, VEGF-C, and proteins of the mToR pathway before and after androgen deprivation therapy in prostate carcinoma: significant decrease after treatment

Abstract

Targeted therapy in hormone refractory prostate cancer (HRPC) is currently under evaluation in many trials. The effect of androgen deprivation therapy (ADT) on many targets in prostate cancer is incompletely known. For the first time, immunohistochemical expression of the platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), vascular endothelial growth factor C (VEGF-C), mammalian target of rapamycin (mToR), p70 ribosomal protein S6 kinase 1 (PS6K), human epidermal growth factor receptor 2 (c-erbB-2), and carbonic anhydrase IX (CA9) was evaluated in 44 patients with prostate carcinoma treated with or without ADT, at biopsy time and after radical prostatectomy. PDGFR, VEGF-C, mToR, and PS6K expression was significantly reduced (p = 0.002, p = 0.035, p = 0.025, and p = 0.033, respectively) after ADT, whereas expression of EGFR, c-erbB-2, and CA9 was not influenced by ADT. In conclusion, targeting PDGFR, VEGF-C, mToR, or PS6K after ADT should be considered with precaution, as those targets can severely be altered or functionally deregulated by ADT.

Changes in Lymphangiogenesis and Vascular Endothelial Growth Factor Expression by Neo‐Adjuvant Hormonal Therapy in Prostate Cancer Patients

“…Our result that VEGF-C expression was increased by NHT in human prostate cancer tissue was confirmed in an androgen-dependent prostate cancer cell line, in accordance with a previous report that VEGF-C is upregulated by androgen depletion in LNCaP cells [24,25]. However, in human prostate cancer tissue, VEGF-C expression was found to be lower in RP as compared to biopsy specimens [26]. We speculate that the discrepancy between these results and ours is due to differences in methodology, including the antibody used and incubation time as well as the analytical method that was applied.…”

“…We speculate that the discrepancy between these results and ours is due to differences in methodology, including the antibody used and incubation time as well as the analytical method that was applied. In addition, the duration of NHT differed between the two studies; the mean duration of NHT was approximately 3 months in the earlier study, since mean interval between diagnosis and prostatectomy was reportedly 119 days . In contrast, the mean duration in our study population was 9.1 months.…”

STAT3 regulated ARF expression suppresses prostate cancer metastasis

“…Staining for SA-ß-Gal activity was performed according to the manufacturer's protocol (Cell Signaling, #9860). We used PTEN 63 and AR (1:250; DAKO, AR441) 64 antibodies validated for FFPE IHC. The STAT3 antibody was validated using SW620 colon cancer xenografts with shRNA-mediated knockdown ( Supplementary Fig.…”

Sunitinib reduces tumor hypoxia and angiogenesis, and radiosensitizes prostate cancer stem‐like cells

“…Sunitinib is a potent inhibitor of tyrosine kinase receptors, such as VEGFRs and PDGFRs, currently used for the treatment of metastatic renal clear cell carcinoma and gastrointestinal stromal tumors . Since many prostate cancers overexpress these growth factor receptors and Sunitinib has been suggested as a therapeutic option for patients with VEGFR +/PDGFR + tumors, we decided to analyze the effect of this drug in preclinical in vitro and in vivo models of prostate cancer.…”