Identification and characterization of blood group A-modified glycoproteins in pancreatic cancer
General Material Designation
[Thesis]
First Statement of Responsibility
C. S. Schaffert
Subsequent Statement of Responsibility
W. G. Chaney
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
University of Nebraska Medical Center
Date of Publication, Distribution, etc.
1996
PHYSICAL DESCRIPTION
Specific Material Designation and Extent of Item
205
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
Ph.D.
Body granting the degree
University of Nebraska Medical Center
Text preceding or following the note
1996
SUMMARY OR ABSTRACT
Text of Note
Pancreatic cancer is one of the most lethal cancers, having a five year survival rate of 3%, due in part to the late stage of the cancer at the time of diagnosis. To aid in the earlier diagnosis of pancreatic cancer, a hamster model has been developed. After treatment with N-nitrosobis(2-oxopropyl)amine (BOP), Syrian hamsters develop ductal pancreatic adenocarcinomas which are morphologically, immunologically, histochemically, biologically and genetically similar to the human disease. This dissertation work involved analyzing similarities in Asn-linked oligosaccharide processing between hamster and human pancreatic cancer, using the blood group A (BGA) antigen as the determinant. It also involved identifying and characterizing BGA-modified glycoproteins (Pancreas Cancer Associated Proteins (PCAP) -3 and -4) in hamster pancreatic cancer and exploring their utility as potential early diagnostic markers for pancreatic cancer. PCAP-3 was identified as galactoprotein b3 (Gap b3), a hamster homolog of the human usd\alphausd3 subunit of integrin very late antigen 3 (VLA-3). VLA-3 was previously examined in pancreatic cancer, but its expression was not altered from normal. PCAP-4 was identified as a homolog of human Mac-2 binding protein (Mac-2-BP) and murine cyclophilin C associated protein/murine adherent macrophage (CyCAP/MAMA). Like Mac-2-BP, PCAP-4 is a ligand for galectin-3. Both galectin-3 and Mac-2-BP are thought to be involved in immune system functions and altered levels of both have been identified in various cancers. The present studies have localized Mac-2-BP to ductal and islet cells and galectin-3 to ductal cells in normal, pancreatitis and cancerous pancreatic tissue. The expression of both proteins increases after onset of either disease, suggesting they may be involved in inflammation or tumorigenesis. In addition, serum Mac-2-BP levels were analyzed and were determined to be significantly elevated in a number of patients diagnosed with acute pancreatitis and pancreatic cancer, further supporting its role in a host inflammatory response.