Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

Abstract

BackgroundExtracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC).MethodsMMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia.ResultsMMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005).ConclusionWe have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer

“…The present findings are consistent with previous studies, which suggested that MMP-9 plays a role in bladder cancer (56,57). The present study identified that the expression rates of MMP-9 in bladder cancer patients was significantly increased compared with healthy control individuals (6,9).…”

Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts of breast invasive ductal cancer

“…Furthermore, the differentially expressed genes in CAFs following treatment with chemotherapy may be important in modulating the function of tumor cells, and subsequently participate in chemoresistance correspondingly. Based the present study, IL8, a multifunctional chemokine secreted by multiple cell types (including monocytes, endothelial cells, fibroblasts and tumor cells), has been frequently reported to be closely associated with cancer development and poor prognosis (7,8,18). The exact role of IL8 in regulating tumor cell behavior remains unclear.…”

Inhibition of gelatinase activity of MMP-2 and MMP-9 by extracts of Bauhinia ungulata L.

“…The expression of MMP-9 and MMP-2 has been implicated in the development and progression of many neoplasms, such as prostate, colorectal, and lung cancer (REIS et al, 2012). Mantena et al (2005) showed that green tea polyphenols are promising as anticarcinogenic agents because these compounds prevent the development of solar UV radiationinduced skin cancer and reduce the expression of MMP-9 and MMP-2.…”

“…Within the family of human MMPs, the matrix metalloproteinase 2 (MMP-2) (gelatinase A, 72 kDa) and matrix metalloproteinase 9 (MMP-9) (gelatinase B, 92 kDa) cleave, among other components, type IV collagen and gelatin, which are the main structural components of the basal membrane (REIS et al, 2012). With the exception of membrane-type MMPs, these enzymes are secreted as latent pro-enzymes and are usually regulated by endogenous tissue inhibitors of the matrix metalloproteinase (TIMPs) (WALTER et al, 2005).…”