Opioid growth factor modulates angiogenesis

Blebea, John; Mazo, J. E.; Kihara, Todd K.; Vu, Jonathan-Hien; McLaughlin, Patricia J.; Atnip, Robert G.; Zagon, Ian S.

doi:10.1067/mva.2000.107763b

Cited by 73 publications

(58 citation statements)

References 25 publications

(41 reference statements)

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“…Because OGF depresses DNA synthesis and subsequent cell/tissue growth in a wide variety of normal and developing cells in humans and animals, including ectodermal, mesodermal, and endodermal derivatives Hauser and Stiene-Martin, 1991;Isayama et al, 1991;Zagon and McLaughlin, 1991;Zagon et al, 1994Zagon et al, , 1995bZagon et al, , 1996aZagon et al, ,b, 1997Zagon et al, , 1999bMcLaughlin, 1996;Vertes et al, 1996;McLaughlin and Wu, 1998;Blebea et al, 2000Blebea et al, , 2002Wilson et al, 2000;Kornyei et al, 2003), the question arises as to the mechanism of peptide action on the cell cycle in these cells. The present investigation examined the specific target(s) in the cell cycle for the OGF-OGFr axis in cells derived from four normal human tissues: umbilical vein endothelial This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -07-0681) on October 15, 2008. cells (HUVECs), epidermal keratinocytes (NHEKs), dermal fibroblasts (NHDFs), and mesenchymal stem cells (hMSCs).…”

Section: Introductionmentioning

confidence: 99%

“…OGF is a constitutively expressed native opioid that is autocrine produced and secreted to inhibit the growth of both normal cells McLaughlin, 1987, 1991;Hauser et al, 1990;Stiene-Martin and Hauser, 1990;Hauser and Stiene-Martin, 1991;Isayama et al, 1991;Villiger and Lotz, 1992;Zagon et al, 1994Zagon et al, , 1995aZagon et al, ,b, 1996aZagon et al, , 1997aZagon et al, ,b, 1998Zagon et al, , 1999bZagon et al, , 2000bMcLaughlin, 1996;Vertes et al, 1996;McLaughlin and Wu, 1998;Blebea et al, 2000;Wilson et al, 2000;Kornyei et al, 2003;Robertson and Andrew, 2003;Malendowicz et al, 2005) and cancer cells (Zagon et al, 1996c;Cheng et al, 2007Cheng et al, , 2008. The action of OGF is tonic, stereospecific, reversible, noncytotoxic, and nonapoptotic inducing, is not associated with differentiative, migratory, invasive, or adhesive processes, is independent of serum, anchorage-independent and occurs at physiologically relevant concentrations (Zagon et al, , 2007a, 2004.…”

Section: Introductionmentioning

confidence: 99%

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The OGF–OGFr Axis Utilizes the p16^INK4aand p21^WAF1/CIP1Pathways to Restrict Normal Cell Proliferation

Fan

McLaughlin

Verderame

et al. 2009

MBoC

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106

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The OGF–OGFr Axis Utilizes the p16^INK4aand p21^WAF1/CIP1Pathways to Restrict Normal Cell Proliferation

Fan

McLaughlin

Verderame

et al. 2009

MBoC

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106

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“…Opioids and opioid receptors were reported to exist in blood vessels in the later stage rat embryo (embryonic day [E]Ϫ16) through adult. 8,9 The addition of opioid peptides inhibited angiogenesis in a chick chorioallantoic membrane model 10 and DNA synthesis in rat vascular walls. 8 In the adult, the endogenous opioid system has been shown to be active in hemodynamic and cardiovascular responses, such as hemorrhagic shock, sepsis, and trauma.…”

Section: Introductionmentioning

confidence: 99%

The κ opioid system regulates endothelial cell differentiation and pathfinding in vascular development

Yamamizu

Furuta

Katayama

et al. 2011

Blood

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The opioid system (opioid peptides and receptors) regulates a variety of neurophysiologic functions, including pain control. Here we show novel roles of the opioid system in vascular development. IntroductionOpioids are defined by their ability to bind to and influence opioid receptors on cell membranes. Three opioid receptors, , ␦, and (MOR, DOR, and KOR), are inhibitory G (Gi) protein-coupled receptors through which endogenous opioids (endorphins, enkephalins, and dynorphins) regulate physiologic functions, such as pain regulation, emotional tone, and reward circuitry. 1 These opioid receptors are the principle physiologic target for most clinically important opioid analgesics, such as morphine. Opioid systems are mainly present in neural tissue and could be involved in neurogenesis during brain development. 2,3 We previously showed that DOR, but not MOR or KOR, plays a crucial role in neurogenesis and neuroprotection in neural stem cells obtained from embryonic C3H mouse forebrain. 4 In recent studies that used embryonic stem (ES) cells, MOR and KOR were shown to promote neural progenitor differentiation and regulate cell specification from neural progenitors. 5,6 Moreover, KOR is highly expressed in human neural precursor cells and functions during neurogenesis in the fetal brain. 7 These results indicate that the opioid systems are involved in neurogenesis from neural stem and progenitor cells.Although endogenous opioids were first characterized in the brain, these opioid systems are found both in neural (brain and spinal cord) and extraneural tissues (ganglia, gut, spleen, stomach, lung, pancreas, liver, heart, blood, and blood vessels). Opioids and opioid receptors were reported to exist in blood vessels in the later stage rat embryo (embryonic day [E]Ϫ16) through adult. 8,9 The addition of opioid peptides inhibited angiogenesis in a chick chorioallantoic membrane model 10 and DNA synthesis in rat vascular walls. 8 In the adult, the endogenous opioid system has been shown to be active in hemodynamic and cardiovascular responses, such as hemorrhagic shock, sepsis, and trauma. 11 The selective opioid receptor agonist U-50,488H has beneficial effects on vascular injury after spinal cord trauma by improving vascular permeability and edema. 12 These findings suggest that the opioid system plays an important role in vascular functions though its physiologic roles and molecular mechanisms remain largely unknown.VEGF/VEGF receptor-2 (fetal liver kinase 1; Flk1) signaling is a key regulator of vascular development during embryogenesis. A VEGF coreceptor, Neuropilin1 (NRP1), is largely coexpressed with Flk1 in vascular progenitors and forms a specific and sensitive receptor for VEGF 164 , an isoform of VEGF. 13,14 The Flk1-VEGF 164 -NRP1 complex potently enhances Flk1 signaling in vascular development. 13 NRP1 is also expressed in particular classes of developing neurons and functions as a receptor for class 3 semaphorins by forming a heterodimer with plexins. [15][16][17] PlexinD1 and semaphorin regulate not onl...

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“…To date, very few studies have investigated the effects of opioids on tumor cell-induced angiogenesis-an essential process mediating tumor growth. Based on previous studies showing morphine's inhibition on hypoxiainduced VEGF expression 11 and blood vessel proliferation, [12][13] we hypothesized that morphine will also inhibit tumor cell-induced angiogenesis to suppress tumor growth and progression in mice. Naltrexone, a classical opioid receptor antagonist, has been suggested as an effective cancer therapeutic, 23 and it is therefore important to address whether morphine commonly prescribed to cancer patients for pain relief can cause further detriment to these patients by increasing tumor growth through effects involving angiogenesis.…”

mentioning

confidence: 99%

“…11 In addition, natural opioid ligands, such as ␤-endorphins, have also been shown to inhibit blood vessel proliferation and to produce shorter vessels when compared with placebo controls using a chicken chorion-allantoic membrane model. [12][13] Adaptive responses to hypoxia are under the control of hypoxia-inducible transcription factors (HIF). HIF-1 activates genes such as VEGF and VEGF-receptor transcription through the binding of hypoxic response elements (HRE) within gene promoter regions.…”

mentioning

confidence: 99%

Morphine Suppresses Tumor Angiogenesis through a HIF-1α/p38MAPK Pathway

Koodie

Ramakrishnan

Roy

2010

The American Journal of Pathology

109

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Morphine, a highly potent analgesic agent, is frequently prescribed for moderate to severe cancer pain. In this study, morphine was administered at a clinically relevant analgesic dose to assess tumor cell-induced angiogenesis and subcutaneous tumor growth in nude mice using mouse Lewis lung carcinoma cells (LLCs). Implantation of mice with a continuous slow-release morphine pellet achieved morphine plasma levels within 250 -400 ng/ml (measured using a radioimmunoassay, Coat-ACount Serum Morphine) and was sufficient to significantly reduce tumor cell-induced angiogenesis and tumor growth when compared with placebo treatment. Morphometric analysis for blood vessel formation further confirmed that morphine significantly reduced blood vessel density (P < 0.003), vessel branching (P < 0.05), and vessel length (P < 0.002) when compared with placebo treatment. Morphine's effect was abolished in mice coadministered the classical opioid receptor antagonist, naltrexone, and in mu-opioid receptor knockout mice, supporting the involvement of the classical opioid receptors in vivo. Morphine's inhibitory effect is mediated through the suppression of the hypoxia-induced mitochondrial p38 mitogen-activated protein kinase (MAPK) pathway. Our results suggest that in vitro morphine treatment of LLCs inhibits the hypoxia-induced nuclear translocation of hypoxiainducible transcription factor 1␣ to reduce vascular endothelial growth factor transcription and secretion, in a manner similar to pharmacological blockade with the p38 MAPK-specific inhibitor, SB203585. These studies indicate that morphine, in addition to its analgesic function , may be exploited for its antiangiogenic potential. Pain management is a serious problem in patients with cancer. Morphine is considered the "gold standard" for relieving pain and is currently one of the most effective drugs available clinically for the management of moderate to severe pain associated with cancer.

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Opioid growth factor modulates angiogenesis

Abstract: These results demonstrate for the first time that endogenous opioids modulate in vivo angiogenesis. Opioid growth factor is a tonically active peptide that has a receptor-mediated action in regulating angiogenesis in developing endothelial and mesenchymal vascular cells.

Cited by 73 publications

References 25 publications

The OGF–OGFr Axis Utilizes the p16^INK4aand p21^WAF1/CIP1Pathways to Restrict Normal Cell Proliferation

The OGF–OGFr Axis Utilizes the p16^INK4aand p21^WAF1/CIP1Pathways to Restrict Normal Cell Proliferation

The κ opioid system regulates endothelial cell differentiation and pathfinding in vascular development

Morphine Suppresses Tumor Angiogenesis through a HIF-1α/p38MAPK Pathway

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Opioid growth factor modulates angiogenesis

Abstract: These results demonstrate for the first time that endogenous opioids modulate in vivo angiogenesis. Opioid growth factor is a tonically active peptide that has a receptor-mediated action in regulating angiogenesis in developing endothelial and mesenchymal vascular cells.

Cited by 73 publications

References 25 publications

The OGF–OGFr Axis Utilizes the p16INK4aand p21WAF1/CIP1Pathways to Restrict Normal Cell Proliferation

The OGF–OGFr Axis Utilizes the p16INK4aand p21WAF1/CIP1Pathways to Restrict Normal Cell Proliferation

The κ opioid system regulates endothelial cell differentiation and pathfinding in vascular development

Morphine Suppresses Tumor Angiogenesis through a HIF-1α/p38MAPK Pathway

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Resources

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The OGF–OGFr Axis Utilizes the p16^INK4aand p21^WAF1/CIP1Pathways to Restrict Normal Cell Proliferation

The OGF–OGFr Axis Utilizes the p16^INK4aand p21^WAF1/CIP1Pathways to Restrict Normal Cell Proliferation