ABSTRACT
The detection of malignant cells in fine-needle aspirates (FNA's) using marker genes is hampered by the fact that these markers are only expressed by certain malignancies or lack sensitivity and/or specificity. Here we report the results of a prospective pilot study examining the expression of KOC (KH-domain containing protein over expressed in cancer), a novel onco-foetal gene, in 76 patients who underwent fine-needle aspiration for further diagnosis of abdominal lesions, aszites, cysts or cerebrospinal fluid. Aspirates were examined by cytology and by a KOC RT-PCR assay. KOC expression was a highly sensitive and specific indicator of malignancy. The KOC assay could be useful to facilitate screening for malignant disease and to improve the diagnostic accuracy of FNAs.
Subject(s)
Pancreatic Neoplasms/genetics , RNA-Binding Proteins/genetics , Biopsy, Needle , Humans , Neoplasm Proteins , Pancreatic Neoplasms/pathology , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Tumor Cells, CulturedABSTRACT
INTRODUCTION: The extracellular matrix (ECM) plays a salient role for proliferation and differentiation of epithelial cells. It was demonstrated that cell-ECM interactions mediated through integrins control gene expression and the tissue phenotype even in malignant tumors. Alterations of the ECM are a key feature of ductal adenocarcinoma of the pancreas. AIMS: To examine the role of integrins and related signaling events for differentiation. METHODOLOGY AND RESULTS: We established an in vitro model for ECM-induced differentiation of poorly differentiated pancreatic carcinoma cells and found that a specific pattern of ECM proteins resembling basal laminas (matrigel) induces differentiation of the PaTu-II pancreatic carcinoma cell line to a ductal phenotype. Both beta1- and beta4-integrins are required for cellular differentiation. Integrin-associated signaling events include activation of pp125 focal adhesion kinase (FAK) and mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinases (ERKs) and c-Jun NH2-terminal kinases (JNKs). However, beta1- and beta4-integrin-mediated differentiation of PaTu-II cells was independent from FAK, ERK, and JNK activation levels. Inhibition of MAPK kinases by PD98059 led to a reduction of proliferation but did not interfere with cellular differentiation of PaTu-II cells on matrigel. CONCLUSION: The integrin-mediated differentiation of PaTu-II cells is regulated and maintained through FAK- and MAPK-independent signal transduction pathways.
