Analysis of <i>EPC‐1</i> growth state–dependent expression, specificity, and conservation of related sequences

Pignolo, Robert J.; Rotenberg, Mitch O.; Cristofalo, Vincent J.

doi:10.1002/jcp.1041620113

Cited by 36 publications

(39 citation statements)

References 45 publications

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“…30 In addition, PEDF has also demonstrated the capacity to promote cell differentiation in neuroblastoma 21 and prostate carcinoma cells, 31 although the mechanism by which this occurs is unknown. In bone, we have previously shown that PEDF is temporally expressed during endochondral bone formation, which suggests that PEDF has a key regulatory role in osteoblastic differentiation.…”

Section: Discussionmentioning

confidence: 99%

Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis

Dass

Contreras

et al. 2007

Cancer Gene Ther

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Despite significant improvements, the current management of primary osteosarcoma is still limited by the development of metastatic disease, which occurs in approximately 30% of patients despite aggressive multiagent chemotherapy and tumor-ablative surgery. Therefore, there is a need for the development of novel agents to improve the outcome of these patients. Pigment epithelium-derived factor (PEDF) has been shown to be one of the most potent inhibitors of angiogenesis, and more recently has demonstrated a functional role in tumor growth, invasion and metastasis. In this study we report, for the first time, the multitargeted role of PEDF in the inhibition of growth, angiogenesis and metastasis of two orthotopic models of osteosarcoma (rat UMR 106-01 and human SaOS-2). Through stable plasmid-mediated gene transfer of full-length human PEDF, we show that PEDF overexpression significantly reduced tumor cell proliferation (Po0.05) and Matrigel invasion (UMR PEDF , Po0.001; SaOS PEDF , Po0.05) and increased adhesion to collagen type-1 (Po0.01), in vitro. In vivo, PEDF overexpression dramatically suppressed orthotopic osteosarcoma growth (Po0.05) and the development of spontaneous pulmonary metastases (UMR PEDF , Po0.05; SaOS PEDF , Po0.001). Furthermore, PEDF-overexpressing tumors exhibited reduced intratumoral angiogenesis, evidenced by a significant decrease in microvessel density (Po0.05). Therefore, together these results suggest that PEDF may be a new and promising approach for the treatment of osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis

Dass

Contreras

et al. 2007

Cancer Gene Ther

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“…4,5,16 In fibroblasts, PEDF inhibits S-phase entry, whereas its absence allows for DNA replication and cel-lular proliferation. 5,17 Genetic deletion of PEDF in mice supports this role. PEDF-null mice display stromal expansion in several organs, including the pancreas and liver.…”

mentioning

confidence: 89%

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Schmitz

Protiva

Gattu

et al. 2011

The American Journal of Pathology

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Pigment epithelium-derived factor (PEDF) is important for maintaining the normal extracellular matrix. We hypothesized that the initiation of pancreatic fibrosis is dependent on the loss of PEDF. Pancreatic PEDF expression was assessed in wild-type mice fed either a control or ethanol diet using an intragastric feeding model. Pancreatitis responses were elicited with either a single episode or a repetitive ceruleininduced (50 g/kg, 6 hourly i.p. injections) protocol in wild-type and PEDF-null mice. Quantitative realtime PCR and immunoblotting were performed to assess fibrogenic responses. In wild-type animals, PEDF expression increased with pancreatitis and was more pronounced in mice fed ethanol. Compared with wild-type mice, ␣-smooth muscle actin staining and expression levels of fibrogenic markers (eg, transforming growth factor-␤1, platelet-derived growth factor, collagen I, and thrombospondin-1) were higher in PEDF-null mice at baseline. Sirius red staining revealed more fibrosis in PEDF-null versus wildtype pancreas 1 week after pancreatitis. Differences in tissue fibrosis resolved with longer recovery periods. PEDF overexpression suppressed thrombospondin-1 levels in vitro. Ethanol feeding and experimental pancreatitis increased PEDF expression in wildtype mice. PEDF-null mice, however, demonstrated enhanced early fibrotic responses compared with wildtype mice with pancreatitis. These findings indicate that PEDF acts as a compensatory antifibrotic cytokine in

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“…Although the NH 2 terminus of this protein was blocked, four tryptic peptides showed high homology with the predicted amino acid sequence of human PEDF/early population doubling level cDNA-1 (EPC-1) (8,20). We therefore cloned a cDNA by screening a mouse liver cDNA library with the aid of a probe of 675-base pair nucleotides covering nucleotide positions 443 to 1117 of human PEDF cDNA (8).…”

Section: Identification Of 45-kda Protein As a Collagen-associatedmentioning

confidence: 99%

Isolation, Purification, and Characterization of a Collagen-associated Serpin, Caspin, Produced by Murine Colon Adenocarcinoma Cells

Kozaki

Miyaishi²,

Koiwai

et al. 1998

Journal of Biological Chemistry

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A 45-kDa serpin secreted by a murine colon adenocarcinoma cell line, colon26, was isolated, purified, and characterized. It was found to bind specifically to type I collagen with high affinity and to type III collagen with lower affinity. Immunohistochemical studies of murine embryonic tissues showed a specific distribution of this collagen-associated serpin, named caspin, in relation to the formation of bone, cartilage, teeth, and basement membrane. The expression of caspin in high and low lung metastatic subclones of colon26 cell lines was inversely correlated with their metastatic capacity: low lung metastatic cells secreted higher amounts of caspin than their high lung metastatic counterparts. Caspin also demonstrated high homology with human pigment epithelium-derived factor/early population doubling level cDNA-1, which reportedly induces neuronal differentiation of human retinoblastoma cells and is expressed in association with G 0 growth arrest. These findings suggest that caspin/pigment epithelium-derived factor/early population doubling level cDNA-1 is a novel factor that might play a crucial role in embryogenesis and tumor metastasis through binding to the extracellular matrix.

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Analysis of EPC‐1 growth state–dependent expression, specificity, and conservation of related sequences

Cited by 36 publications

References 45 publications

Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis

Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Isolation, Purification, and Characterization of a Collagen-associated Serpin, Caspin, Produced by Murine Colon Adenocarcinoma Cells

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