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Growth factor mediated signaling in pancreatic pathogenesis.

Nandy D, Mukhopadhyay D - Cancers (Basel) (2011)

Bottom Line: Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis.Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors.However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905, USA. mukhopadhyay.debabrata@mayo.edu.

ABSTRACT
Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

No MeSH data available.


Related in: MedlinePlus

Role of PDGF in formation of pancreatitis, pancreatic carcinoma and progression of cancer.
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f5-cancers-03-00841: Role of PDGF in formation of pancreatitis, pancreatic carcinoma and progression of cancer.

Mentions: The platelet derived growth factor (PDGF) family includes four members: PDGF-A, PDGF-B, PDGF-C, and PDGF-D. These proteins are secreted as homodimer or heterodimer proteins. PDGF receptors are made up of alpha (α) and beta (β) chains. PDGF-A, PDGF-B, and PDGF-C can specifically bind to PDGF-α and -β chain receptors, while PDGF-D binds only to PDGF-β chain receptors [72–74]. To characterize different staging of pancreatic fibrogenesis, Gunter Kloppel's group (2006) designed an elaborate study of human pancreatic specimens. They characterized different stages of disease progression in tissues from patients with alcohol-related chronic pancreatitis (Figure 5). The initial stage was characterized by fibrogenesis. During the initial stages, macrophage and ductal cells are the main sources of TGF-β and PDGF-B, which cause fibroblast activation and proliferation. In the later stages of disease progression, fibrogenesis is slowed due to decreased numbers of macrophages and PDGF-B immunoreactivity. It also has been shown that overexpression of PDGF-D increases migration and invasion of pancreatic cancer cells through matrigel and induces tube formation of human umbilical vein endothelial cells (HUVECs) with the resultant activation of matrix metalloproteinase-9 (MMP-9) and VEGF. Wang and co-workers 2007 describe the positive regulatory role of PDGF-D in migration, invasion and angiogenesis through activation of MMP-9 and VEGF [75].


Growth factor mediated signaling in pancreatic pathogenesis.

Nandy D, Mukhopadhyay D - Cancers (Basel) (2011)

Role of PDGF in formation of pancreatitis, pancreatic carcinoma and progression of cancer.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756392&req=5

f5-cancers-03-00841: Role of PDGF in formation of pancreatitis, pancreatic carcinoma and progression of cancer.
Mentions: The platelet derived growth factor (PDGF) family includes four members: PDGF-A, PDGF-B, PDGF-C, and PDGF-D. These proteins are secreted as homodimer or heterodimer proteins. PDGF receptors are made up of alpha (α) and beta (β) chains. PDGF-A, PDGF-B, and PDGF-C can specifically bind to PDGF-α and -β chain receptors, while PDGF-D binds only to PDGF-β chain receptors [72–74]. To characterize different staging of pancreatic fibrogenesis, Gunter Kloppel's group (2006) designed an elaborate study of human pancreatic specimens. They characterized different stages of disease progression in tissues from patients with alcohol-related chronic pancreatitis (Figure 5). The initial stage was characterized by fibrogenesis. During the initial stages, macrophage and ductal cells are the main sources of TGF-β and PDGF-B, which cause fibroblast activation and proliferation. In the later stages of disease progression, fibrogenesis is slowed due to decreased numbers of macrophages and PDGF-B immunoreactivity. It also has been shown that overexpression of PDGF-D increases migration and invasion of pancreatic cancer cells through matrigel and induces tube formation of human umbilical vein endothelial cells (HUVECs) with the resultant activation of matrix metalloproteinase-9 (MMP-9) and VEGF. Wang and co-workers 2007 describe the positive regulatory role of PDGF-D in migration, invasion and angiogenesis through activation of MMP-9 and VEGF [75].

Bottom Line: Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis.Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors.However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905, USA. mukhopadhyay.debabrata@mayo.edu.

ABSTRACT
Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

No MeSH data available.


Related in: MedlinePlus