Expression of a fibroblast growth factor-binding protein during the development of adenocarcinoma of the pancreas and colon

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 2; pp. 1191 - 1198
• Main Authors: TASSI, Elena, HENKE, Ralf T, BOWDEN, Emma T, SWIFT, Matthew R, KODACK, David P, KUO, Angera H, MAITRA, Anirban, WELLSTEIN, Anton
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.01.2006
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Carrier Proteins - biosynthesis; Carrier Proteins - physiology; Cell Transformation, Neoplastic; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Disease Progression; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Profiling; Humans; In Situ Hybridization; Intercellular Signaling Peptides and Proteins; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Pancreatitis - genetics; Pancreatitis - pathology; Pancrelipase - physiology; Risk Assessment; RNA, Messenger - biosynthesis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Cells, Cultured; Tumors; Up-Regulation; Fibroblast growth factor; Binding protein; Digestive system; Gut; Biological marker; Digestive diseases; Malignant tumor; Monoclonal antibody; Colon; Gene expression; Pancreas adenocarcinoma; Pancreatic disease
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-05-2926

The activity of growth factors is crucial for tumor progression. We previously characterized a secreted fibroblast growth factor-binding protein (FGF-BP1) as a chaperone molecule, which enhances the biological functions of FGFs by releasing FGFs from the extracellular matrix. Here, we characterize the frequency and pattern of FGF-BP1 expression during the malignant progression of pancreas and colorectal carcinoma. For this, we generated monoclonal antibodies that detect FGF-BP1 protein in formalin-fixed, paraffin-embedded tissues and applied in situ hybridization to detect FGF-BP1 mRNA in adjacent tissue sections. FGF-BP1 protein and mRNA were found up-regulated (>70% positive) in parallel (r = 0.70, P < 0.0001) in colon adenoma (n = 9) as well as primary (n = 46) and metastatic (n = 71) colorectal cancers relative to normal colon epithelia (all P < 0.0001, versus normal). Similarly, pancreatitis (n = 17), pancreatic intraepithelial neoplasia (n = 80), and pancreatic adenocarcinoma (n = 67) showed a significant up-regulation of FGF-BP1 compared with normal pancreas (n = 42; all P < 0.0001, relative to normal). Furthermore, the biological activity of FGF-BP1 is neutralized by one of the antibodies, suggesting the potential for antibody-based therapeutic targeting. We propose that the up-regulation of the secreted FGF-BP1 protein during initiation of pancreas and colon neoplasia could make this protein a possible serum marker indicating the presence of high-risk premalignant lesions.