Increased caveolin-1 expression associated with prolonged overall survival rate in hepatocellular carcinoma

Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
Pathology (Impact Factor: 2.19). 08/2010; 42(5):438-45. DOI: 10.3109/00313025.2010.494293
Source: PubMed


Recent study indicates that the binding of caveolin-1 (CAV1), the essential constituent of caveolae, to endothelial nitric oxide synthase (eNOS) prevents nitric oxide (NO) production in cirrhotic human liver. However, their interplay in hepatocellular carcinoma (HCC) remains undetermined.
Paraffin-embedded sections from 73 HCC patients were included in this study. The expression patterns of CAV1 and eNOS determined by immunohistochemistry were correlated with the clinicopathological characteristics and overall survival.
Although CAV1 expression did not correlate with any clinicopathological characteristic, increased CAV1 expression was associated with prolonged overall survival (p = 0.021), even when using the multivariate Cox's regression model (OR = 0.25, 95%CI = 0.08-0.72, p = 0.011). eNOS expression was correlated with an increased histological grade (p = 0.002) and intriguingly, the patients had a decreased overall survival when their lesions presented with high eNOS but low CAV1 expression concomitantly (p = 0.003). Meanwhile, the increased CAV1/eNOS merged level determined by immunofluorescence was significantly associated with a decreased histological grade and better overall survival (p = 0.023 and 0.001, respectively).
Our results suggest CAV1 may play a tumour-suppressive role and can serve as a predictive biomarker in HCC. The impacts of CAV1 on hepatocarcinogenesis may occur partly through its modulation of eNOS.

Download full-text


Available from: Yao-Tsung Yeh, Feb 04, 2015
22 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Caveolins are a family of membrane-bound scaffolding proteins that compartmentalize and negatively regulate signal transduction. Recent studies have implicated a loss of caveolin-1 (Cav-1) expression in the pathogenesis of human cancers. Loss of Cav-1 expression in cancer-associated fibroblasts results in an activated tumor microenvironment, thereby driving early tumor recurrence, metastasis, and poor clinical outcome in breast and prostate cancers. We describe various paracrine signaling mechanism(s) by which the loss of stromal Cav-1 promotes tumor progression, including fibrosis, extracellular matrix remodeling, and the metabolic/catabolic reprogramming of cancer-associated fibroblast, to fuel the growth of adjacent tumor cells. It appears that oxidative stress is the root cause of initiation of the loss of stromal Cav-1 via autophagy, which provides further impetus for the use of antioxidants in anticancer therapy. Finally, we discuss the functional role of Cav-1 in epithelial cancer cells.
    Annual Review of Pathology Mechanisms of Disease 01/2011; 7(1):423-67. DOI:10.1146/annurev-pathol-011811-120856 · 18.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Caveolins are the principal protein component of caveolae, plasma membrane invaginations found in most cell types. Caveolin-1 (Cav-1) plays a major role in oncogenesis through its various functions in lipid transport, membrane trafficking, and signal transduction. Increased expression of Cav-1 in tumor cells has been associated with aggressiveness and poor survival. More recently, loss of stromal Cav-1 expression was linked to poor survival and increased metastatic potential in breast and prostate cancer. To date, there is no study addressing the clinical significance of Cav-1 expression in malignant melanoma (MM). Our study consisted of 44 cases of MM: 12 MM lymph node metastases from patients with short survival, 12 MM lymph node metastases from patients with long survival and 20 primary MM. All cases were stained with Cav-1 antibodies. Cav-1 expression in melanoma and stromal cells was quantified using a 3 point scale: 0 = no staining, 1 = diffuse weak staining or strong staining in < 30% of cells, and 2 = diffuse strong staining. A score of 0-1 represented low Cav-1 expression and a score of 2 represented high Cav-1 expression. In patients with MM lymph node metastases, a low stromal Cav-1 expression was associated with shorter survival when compared to the high stromal Cav-1 expression group (median survival 252 days versus 3,508 days, p value 0.0054). Conversely, high Cav-1 expression in melanoma cells was associated with a longer survival in primary MM (p < 0.0001). In conclusion, high expression of stromal Cav-1 correlates with longer survival in malignant melanoma metastases, and high expression of Cav-1 in melanoma cells correlates with longer survival in primary malignant melanoma.
    Cell cycle (Georgetown, Tex.) 12/2011; 10(24):4250-5. DOI:10.4161/cc.10.24.18551 · 4.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heart damage induced by chlorpromazine (CPZ) toxicity is associated with changes in the expression of various enzymes and proteins. This study aimed to investigate CPZ‑induced alterations in cardiac E-cadherin and caveolin-1 (cav-1) after CPZ administration. Male Wistar rats were randomly divided into two groups: a control group and a CPZ group. The CPZ group was administered CPZ intraperitoneally at a single dose of 10 mg/kg for 21 days; the controls were given the same amount of saline via the same route. On Day 22, the rats were anesthetized, and a thoracotomy was performed in all animals. Immunohistochemical analysis was performed to evaluate protein expression of E-cadherin and cav-1. Sections were analyzed by digital image analysis. Results of the present study revealed that cardiac protein expression of E-cadherin and cav-1 was altered after CPZ-induced toxicity in the rat. The expression of E-cadherin was significantly reduced, while expression of cav-1 was significantly increased after CPZ treatment, as supported by integrated optical density analysis, compared with the control (P<0.05). The current findings indicate that such changes in the expression of E-cadherin and cav-1 may be reflected in abnormal cardiac function, and these proteins may be useful in revealing the mechanisms underlying CPZ-induced toxicity and may also provide additional insight for further research.
    Molecular Medicine Reports 12/2011; 5(3):705-9. DOI:10.3892/mmr.2011.729 · 1.55 Impact Factor
Show more