Osteopontin and Interleukin-8 Expression is Independently Associated with Prostate Cancer Recurrence

Abstract

Purpose: Lack of reliable biomarkers limits accurate prediction of prostate-specific antigen biochemical recurrence (disease progression) in prostate cancer. The two inflammatory chemokines, osteopontin and interleukin-8 (IL-8), are associated with tumor angiogenesis and metastasis. We investigated whether osteopontin and IL-8 expression in prostate cancer correlates with disease progression. Experimental Design: Archival prostatectomy specimens (n = 103) were obtained from patients with minimum 72-month follow-up. Osteopontin and IL-8 expression was evaluated by immunohistochemistry and graded for intensity and the area. Association of osteopontin and IL-8 staining with biochemical recurrence was evaluated by univariate and multivariate models. Results: In tumor cells, osteopontin and IL-8 staining was higher in the recurred group (203.2 F 78.4; 181.1 F 89.3) than in the nonrecurred group (122.7 F 76.6; 96.4 F 85.6; P < 0.001). Higher osteopontin and IL-8 staining was also observed in benign areas adjacent to tumor in the recurred group, than in nonrecurred group. In univariate analysis, except age, all preoperative and postoperative variables and osteopontin and IL-8 staining scores were significantly associated with biochemical recurrence (P < 0.05). In multivariate analysis, margin status and osteopontin staining independently associated with biochemical recurrence within 72 months. Osteopontin, either alone or with IL-8 and seminal vesicle invasion, was a significant variable in predicting biochemical recurrence within 24 months. Osteopontin and IL-8 staining predicted recurrence with high sensitivity (75.5%; 73.6%) and specificity (76%; 70.6%). Conclusion: In prostatectomy specimens, osteopontin expression is independently associated with biochemical recurrence. Both osteopontin and IL-8 may be predictors of early disease progression.

Predominant Expression of CCL2 at the Tumor Site of Prostate Cancer Patients Directs a Selective Loss of Immunological Tolerance to CCL2 That Could Be Amplified in a Beneficial Manner

“…Several recent studies have shown that chemokines, in particular CXCL12 (SDF-1a), CXCL8 (IL-8), CCL2 (MCP-1), CCL3, (MIP-1a), CCL5 (RANTES), and CXCL10 (IP-10), are produced at the tumor site by the CaP cells that also express their receptors, and commonly also by the supporting tissue (11)(12)(13)(14)(15)(16)(17). These chemokines are likely to promote tumor development and angiogenesis (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer

“…Interleukin-8 expression has been shown to be elevated in CaP tissue by immunohistochemistry (Huang et al, 2005;Murphy et al, 2005) and by in situ hybridisation (Uehara et al, 2005), whereas overexpression of IL-8 has been detected in the serum of CaP patients (Veltri et al, 1999;McCarron et al, 2002). Furthermore, IL-8 expression in CaP tissue has been associated with increased biochemical recurrence (Caruso et al, 2008). Consistent with this, studies in athymic mice have correlated the increased expression of IL-8 in implanted human CaP cells with increased vascularisation of the tumours and an enhanced tumourigenic and metastatic potential (Inoue et al, 2000;Kim et al, 2001).…”

Upregulation of Drug Transporter Expression by Osteopontin in Prostate Cancer Cells

“…OPN is experimentally demonstrated to play a crucial role in tumor models of progression, invasion, and metastasis (Bussard et al, 2008). Clinically elevated levels of circulating OPN in cancer patients are correlated to increased metastasis and poor prognosis in many solid tumors, including breast, liver, head, and neck (Bramwell et al, 2006;Khodavirdi et al, 2006;Caruso et al, 2008;Mack et al, 2008;Li et al, 2012). Among patients with prostate cancer, high serum levels of OPN correlate to a high rate of metastasis to bone (Hotte et al, 2002;Bonfil et al, 2007;Ramankulov et al, 2007).…”