Latexin exhibits tumor-suppressor potential in pancreatic ductal adenocarcinoma

Abstract

Recent studies suggest that latexin (Lxn) expression is involved in stem cell regulation and that it plays significant roles in tumor cell migration and invasion. The clinicopathological significance of Lxn expression and its possible correlation with CD133 expression in pancreatic ductal adenocarcinoma (PDAC) is currently unknown. In the present study, immunohistochemical analysis was performed to determine Lxn and CD133 expression in 43 PDAC patient samples and in 32 corresponding adjacent non-cancerous samples. The results were analyzed and compared with patient age, gender, tumor site and size, histological grade, clinical stage and overall mean survival time. Lxn expression was clearly decreased in the PDAC tissues compared with that in the adjacent non-cancerous tissues, while CD133 expression was increased. Low Lxn expression in the PDAC tissues was significantly correlated with tumor size (P=0.002), histological grade (P=0.000), metastasis (P=0.007) and clinical stage (P=0.018), but not with age (P=0.451), gender (P=0.395) or tumor site (P=0.697). Kaplan-Meier survival analysis revealed that low Lxn expression was significantly correlated with reduced overall survival time (P=0.000). Furthermore, Lxn expression was found to be inversely correlated with CD133 expression (r=−0.485, P=0.001). Furthermore, CD133-positive MIA PaCa-2 pancreatic tumor cells were sorted by magnetic-activated cell sorting (MACS), and those that overexpressed Lxn exhibited a significantly higher rate of apoptosis and lower proliferative activity. Our findings suggest that Lxn may function as a tumor suppressor that targets CD133-positive pancreatic cancer cells.

Biochemical characterization of the YBPCI miniprotein, the first carboxypeptidase inhibitor isolated from Yellow Bell Pepper ( Capsicum annuum L). A novel contribution to the knowledge of miniproteins stability

“…In humans, the dysregulated activity of some MCPs has been associated with several diseases such as blood coagulation/ fibrinolysis, inflammation, carcinogenesis, epilepsy and febrile seizures, among others [1,2,4,5]. According to these studies, the use of protease inhibitors (PIs) in order to regulate MCPs action has emerged as a potential tool for the development of therapeutic strategies for a large number of diseases; as anticarcinogenic, anti-angiogenic and antithrombotic, among others [6][7][8][9]. Furthermore, although protease inhibitors have been considered only as antinutritional factors, they have regained interest in recent years because of their potential for drug development and positive dietary effects.…”

High Rab11-FIP4 expression predicts poor prognosis and exhibits tumor promotion in pancreatic cancer

“…The Rab11-FIP4 expression in the pancreatic tumor samples was independently assessed by two clinical pathologists. Immunohistochemical evaluation of the Rab11-FIP4 protein was performed according to previously described methods, taking into account the extent (graded from 0 to 4) and intensity (0–3) of immunopositivity (17,18). We multiplied the intensity score with positive extent to define the final score, and a final score range was 0–12.…”

The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy

“…1D ). LXN expression has been reported to be repressed in many solid tumours including thyroid, hepatic and pancreatic carcinomas 13 , 15 , 21 . To understand whether the same expression patterns were observed in normal versus malignant prostate, we homogenised several normal and several high Gleason (>G8) grade prostate tissue specimens and compared the protein expression of LXN via Western blotting (Fig.…”

“…Several additional studies have also linked loss of LXN expression with numerous human malignancies, such as leukeamia 11 , melanoma 12 , hepatocellular carcinoma 13 and pancreatic ductal adenocarcinoma (PDAC) 14 . For example, LXN expression was shown to significantly correlate with tumour size, histological grade, metastasis and clinical stage in PDAC, indicating that LXN may function as a tumour suppressor 15 . Despite its association with numerous malignancies, the normal function of LXN and subsequently its role in malignant progression remain enigmatic.…”