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Connective tissue growth factor in tumor pathogenesis.

Jacobson A, Cunningham JL - Fibrogenesis Tissue Repair (2012)

Bottom Line: This discrepancy is not yet understood.High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon.Despite this, they are malignant and most patients have metastatic disease at diagnosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Osteoporosis and Clinical Pharmacogenetics, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

ABSTRACT
Key roles for connective tissue growth factor (CTGF/CCN2) are demonstrated in the wound repair process where it promotes myofibroblast differentiation and angiogenesis. Similar mechanisms are active in tumor-reactive stroma where CTGF is expressed. Other potential roles include prevention of hypoxia-induced apoptosis and promoting epithelial-mesenchymal transistion (EMT). CTGF expression in tumors has been associated to both tumor suppression and progression. For example, CTGF expression in acute lymphoblastic leukemia, breast, pancreas and gastric cancer correlates to worse prognosis whereas the opposite is true for colorectal, lung and ovarian cancer. This discrepancy is not yet understood. High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon. These tumors maintain a high grade of differentiation and low proliferation. Despite this, they are malignant and most patients have metastatic disease at diagnosis. These tumors demonstrate several phenotypes potentially related to CTGF function namely: cell migration, absent tumor cell apoptosis, as well as, reactive and well vascularised myofibroblast rich stroma and fibrosis development locally and in distal organs. The presence of CTGF in other endocrine tumors indicates a role in the progression of well-differentiated tumors.

No MeSH data available.


Related in: MedlinePlus

A: Full length CTGF contains 4 modules: insulin-like growth factor binding protein-like (IGFBP), von Willebrand factor type-C repeat (VWF), thrombospondin type 1 repeat (TSP-1) and C-terminal cystine knot (cys-knot). Arrows indicate potential cleavage sites. B: Ileal carcinoid tissue immunostained with antibodies to CTGF (A), α-SMA (B) and CD31/CD34 (C) identifies vascular endothelial cells demonstrating typical tumour cell IR for CTGF and stromal expression of α-SMA detected both in myofibroblasts and in vascular smooth muscle cells.
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Figure 1: A: Full length CTGF contains 4 modules: insulin-like growth factor binding protein-like (IGFBP), von Willebrand factor type-C repeat (VWF), thrombospondin type 1 repeat (TSP-1) and C-terminal cystine knot (cys-knot). Arrows indicate potential cleavage sites. B: Ileal carcinoid tissue immunostained with antibodies to CTGF (A), α-SMA (B) and CD31/CD34 (C) identifies vascular endothelial cells demonstrating typical tumour cell IR for CTGF and stromal expression of α-SMA detected both in myofibroblasts and in vascular smooth muscle cells.

Mentions: CTGF is a 349-amino acid polypeptide consisting of four domains (see Figure 1A). Full length CTGF has an estimated molecular weight of 33 kD while cleavage in the hinge region produces N- and C-terminal fragments with an estimated molecular weight of 20-23 kD and these fragments may have specific biological functions [4,5]. Different cellular sources may offer different proteases for CTGF processing, thus forming a subset of fragments, which in turn determines CTGF action. It is speculated that CTGF may even promote its own proteolysis in some tissues, resulting in differential retention of a specific fragment [6]. High levels of N-terminal CTGF are found in patients with fibrotic scleroderma [7] and in diabetic patients with nephropathy [8].


Connective tissue growth factor in tumor pathogenesis.

Jacobson A, Cunningham JL - Fibrogenesis Tissue Repair (2012)

A: Full length CTGF contains 4 modules: insulin-like growth factor binding protein-like (IGFBP), von Willebrand factor type-C repeat (VWF), thrombospondin type 1 repeat (TSP-1) and C-terminal cystine knot (cys-knot). Arrows indicate potential cleavage sites. B: Ileal carcinoid tissue immunostained with antibodies to CTGF (A), α-SMA (B) and CD31/CD34 (C) identifies vascular endothelial cells demonstrating typical tumour cell IR for CTGF and stromal expression of α-SMA detected both in myofibroblasts and in vascular smooth muscle cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368788&req=5

Figure 1: A: Full length CTGF contains 4 modules: insulin-like growth factor binding protein-like (IGFBP), von Willebrand factor type-C repeat (VWF), thrombospondin type 1 repeat (TSP-1) and C-terminal cystine knot (cys-knot). Arrows indicate potential cleavage sites. B: Ileal carcinoid tissue immunostained with antibodies to CTGF (A), α-SMA (B) and CD31/CD34 (C) identifies vascular endothelial cells demonstrating typical tumour cell IR for CTGF and stromal expression of α-SMA detected both in myofibroblasts and in vascular smooth muscle cells.
Mentions: CTGF is a 349-amino acid polypeptide consisting of four domains (see Figure 1A). Full length CTGF has an estimated molecular weight of 33 kD while cleavage in the hinge region produces N- and C-terminal fragments with an estimated molecular weight of 20-23 kD and these fragments may have specific biological functions [4,5]. Different cellular sources may offer different proteases for CTGF processing, thus forming a subset of fragments, which in turn determines CTGF action. It is speculated that CTGF may even promote its own proteolysis in some tissues, resulting in differential retention of a specific fragment [6]. High levels of N-terminal CTGF are found in patients with fibrotic scleroderma [7] and in diabetic patients with nephropathy [8].

Bottom Line: This discrepancy is not yet understood.High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon.Despite this, they are malignant and most patients have metastatic disease at diagnosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Osteoporosis and Clinical Pharmacogenetics, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

ABSTRACT
Key roles for connective tissue growth factor (CTGF/CCN2) are demonstrated in the wound repair process where it promotes myofibroblast differentiation and angiogenesis. Similar mechanisms are active in tumor-reactive stroma where CTGF is expressed. Other potential roles include prevention of hypoxia-induced apoptosis and promoting epithelial-mesenchymal transistion (EMT). CTGF expression in tumors has been associated to both tumor suppression and progression. For example, CTGF expression in acute lymphoblastic leukemia, breast, pancreas and gastric cancer correlates to worse prognosis whereas the opposite is true for colorectal, lung and ovarian cancer. This discrepancy is not yet understood. High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon. These tumors maintain a high grade of differentiation and low proliferation. Despite this, they are malignant and most patients have metastatic disease at diagnosis. These tumors demonstrate several phenotypes potentially related to CTGF function namely: cell migration, absent tumor cell apoptosis, as well as, reactive and well vascularised myofibroblast rich stroma and fibrosis development locally and in distal organs. The presence of CTGF in other endocrine tumors indicates a role in the progression of well-differentiated tumors.

No MeSH data available.


Related in: MedlinePlus