Expression of a fibroblast growth factor-binding protein during the development of adenocarcinoma of the pancreas and colon.
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.
Tassi
Elena
E
Lombardi Cancer Center, Georgetown University, 3970 Reservoir Road, Washington, DC 20057, USA.
Henke
Ralf T
RT
Bowden
Emma T
ET
Swift
Matthew R
MR
Kodack
David P
DP
Kuo
Angera H
AH
Maitra
Anirban
A
Wellstein
Anton
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics / Q000473:pathology; D020799:Pancrelipase / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D018570:Risk Assessment; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C070699:FGFBP1 protein, human; D020799:Pancrelipase