TY - JOUR
T1 - Expression of a fibroblast growth factor-binding protein during the development of adenocarcinoma of the pancreas and colon
AU - Tassi, Elena
AU - Henke, Ralf T.
AU - Bowden, Emma T.
AU - Swift, Matthew R.
AU - Kodack, David P.
AU - Kuo, Angera H.
AU - Maitra, Anirban
AU - Wellstein, Anton
PY - 2006/1/15
Y1 - 2006/1/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=31544452499&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31544452499&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-05-2926
DO - 10.1158/0008-5472.CAN-05-2926
M3 - Article
C2 - 16424058
AN - SCOPUS:31544452499
VL - 66
SP - 1191
EP - 1198
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 2
ER -