Influences of the lysosomal associated membrane proteins (Lamp‐1, Lamp‐2) and Mac‐2 binding protein (Mac‐2‐BP) on the prognosis of pancreatic carcinoma

Abstract

BACKGROUND Lamps and Mac‐2‐BP are ligands of galectin‐3, and they were suggested to influence tumor proliferation and metastasis formation. The authors studied the expression of Lamp‐1, Lamp‐2, and Mac‐2‐BP in pancreatic carcinoma and evaluated their influence on patient prognosis. METHODS Northern blot analysis, in situ hybridization, and immunohistochemistry were performed in 12 normal and 28 pancreatic carcinoma tissue samples and in pancreatic carcinoma cell lines. The molecular findings in the tumor samples were correlated with the prognosis and histopathologic tumor characteristics. In addition, in Lamp‐1 transfected CAPAN‐1 pancreatic carcinoma cells, cell proliferation was analyzed. RESULTS Lamp‐1, Lamp‐2, and Mac‐2‐BP were overexpressed in 61% (1.6‐fold increase, not significant), 71% (3.0‐fold increase, P < 0.01), and 93% (5.6‐fold increase, P < 0.01) of the pancreatic carcinoma samples. Lamp‐1 and Lamp‐2 immunoreactivity was present at the luminal side of the ductal carcinoma cells whereas Mac‐2‐BP immunoreactivity was diffusely spread over the whole cytoplasm and the nucleolus of ductal carcinoma cells. Correlation of the molecular data with clinical patient parameters revealed that patients whose tumors exhibited high Lamp‐1 mRNA expression lived significantly longer (median, 17 months) after tumor resection than patients whose tumors exhibited low to moderate Lamp‐1 mRNA levels (median, 8 months; P < 0.02). No relation between Lamp‐2 and Mac‐2‐BP mRNA expression and any of the histopathologic parameters was found. Lamp‐1 transfected CAPAN‐1 cells showed decreased cell growth compared with the nontransfected cells. CONCLUSIONS Lamp‐1 might influence local tumor progression rather than the formation of tumor metastasis in pancreatic carcinoma, whereas Mac‐2‐BP and Lamp‐2 seem to have little influence on these parameters in pancreatic carcinoma. Cancer 2002;94:228–39. © 2002 American Cancer Society.

N-glycoprotein profiling of lung adenocarcinoma pleural effusions by shotgun proteomics

“…23 Finally, lysosome-associated membrane glycoprotein-2 (LAMP-2, CD107b) is highly expressed in lung, protects the lysosomal membrane from autodigestion, and has been implicated in metastasis of pancreatic carcinoma. 12 Cancer development is a multistep process; therefore, different biomarker populations for earlystage (local growth), mid-stage (vessel infiltration), and late-stage disease (metastatic growth) have to be envisioned, each of them characterized by an individual N-glycosylation profile. A malignant pleural effusion from lung adenocarcinoma is, by definition, pT4.…”

Induction of Mac-2BP by nerve growth factor is regulated by the PI3K/Akt/NF-κB-dependent pathway in the HEK293 cell line

“…Supranormal serum levels of Mac-2BP have been found in patients with breast, lung, pancreatic, and gastric tumors, Non-Hodgkin's lymphoma, asthma, and human immunodeficiency virus infection (2)(3)(4)(5)(6)(7)(8)(9). The reported evidence implicates Mac-2BP as a diagnostic and/or prognostic marker of poor outcome in several tumor types.…”

Proteomic Analysis of Temporally Stimulated Ovarian Cancer Cells for Biomarker Discovery

“…Studies of lung endothelial cells have suggested that one manner in which LAMP-1 might facilitate metastasis is via increased translocation to the cell membrane, where it acts as a ligand to galectin-3 (49,50). However, correlation studies performed in patients with pancreatic carcinomas suggest that increased levels of LAMP-1 exhibit improved outcomes post-tumor resection (51). Thus, the exact mechanisms through which LAMP-1 might play a role in cancer cascades are not completely understood.…”