Pro-nerve growth factor in the ovary and human granulosa cells

Meinel, Sabine; Blohberger, J.; Berg, Dieter; Berg, U.; Dissen, Gregory A.; Ojeda, Sergio R.; Mayerhofer, Artur

doi:10.1515/hmbci-2015-0028

Cited by 7 publications

(8 citation statements)

References 43 publications

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“…In contrast, ICIs as single agents have not shown meaningful benefit for proficient MMR tumors (8), which are the vast majority of GI cancer cases. MSI-H tumors account for 6-22% of gastric, 1% of pancreatic, 3% of liver, and 14-16% of colorectal cancers (22)(23)(24)(25)(26)(27). Antibodies against PD-1/programmed death-ligand 1 (PD-L1) or cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) are the most clinically advanced immunotherapy in cancer (12).…”

Section: Introductionmentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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CD73, a cell surface 5 ′ nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

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Section: Introductionmentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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“…We will then present recent data, which implicate necroptotic cell death in GCs and in human CL regression. We will here not discuss studies, which identified further factors of potential relevance to ovarian follicular fate, e.g., handling of catecholamines and generation of H 2 O 2 (5–9).…”

Section: Introduction and Scopementioning

confidence: 99%

Human Luteinized Granulosa Cells—A Cellular Model for the Human Corpus Luteum

Bagnjuk¹,

Mayerhofer²

2019

Front. Endocrinol.

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In the ovary, the corpus luteum (CL) forms a temporal structure. Luteinized mural granulosa cells (GCs), which stem from the ruptured follicle, are the main cells of the CL. They can be isolated from follicular fluid of woman undergoing in vitro fertilization. In culture, human GCs are viable for several days and produce progesterone, yet eventually steroid production stops and GCs with increasing time in culture undergo changes reminiscent of the ones observed during the demise of the CL in vivo . This short review summarizes the general use of human GCs as a model for the primate CL and some of the data from our lab, which indicate that viability, functionality, survival and death of GCs can be regulated by local signal molecules (e.g., oxytocin and PEDF) and the extracellular matrix (e.g., via the proteoglycan decorin). We further summarize studies, which identified autophagocytotic events in human GCs linked to the activation of an ion channel. More recent studies identified a form of regulated cell death, namely necroptosis. This form of cell death may, in addition to apoptosis, contribute to the demise of the human CL. We believe that human GCs are a unique window into the human CL. Studies employing these cells may lead to the identification of molecular events and novel targets, which may allow to interfere with CL functions.

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“…The increase in the biosynthetic enzymes for ACh indicate that NGF regulates ovarian ACh production. Previous reports also suggest that NGF stimulates ACh production (6,9,10). This increase could protect follicular development from the actions of an over-activated sympathetic pathway and chronic increase in ovarian noradrenaline, caused by the hyperinnervation of the organ (39,40).…”

Section: Discussionmentioning

confidence: 80%

“…The nerve growth factor (NGF) was the first neurotrophic factor found to regulate ovarian noradrenergic neurons ( 8 ). NGF is one of the most important factors in the regulation of cholinergic neurons in the central nervous system ( 9 , 10 ), but there is limited information on its action in the ovary. If this is correct, we either can suggest that NGF acting on sympathetic nerves increases NE in the ovary by a direct effect of NGF or induced by stress ( 11 , 12 ) and can participates in the development of the PCO phenotype in rat.…”

Section: Introductionmentioning

confidence: 99%

Nerve Growth Factor: A Dual Activator of Noradrenergic and Cholinergic Systems of the Rat Ovary

et al. 2021

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The functioning of the ovary is influenced by the autonomic system (sympathetic and cholinergic intraovarian system) which contributes to the regulation of steroid secretion, follicular development, and ovulation. There is no information on the primary signal that activates both systems. The nerve growth factor (NGF) was the first neurotrophic factor found to regulate ovarian noradrenergic neurons and the cholinergic neurons in the central nervous system. The aim of this study was to determine whether NGF is one of the participating neurotrophic factors in the activation of the sympathetic and cholinergic system of the ovary in vivo and its role in follicular development during normal or pathological states. The administration of estradiol valerate (a polycystic ovary [PCO] phenotype model) increased norepinephrine (NE) (through an NGF-dependent mechanism) and acetylcholine (ACh) levels. Intraovarian exposure of rats for 28 days to NGF (by means of an osmotic minipump) increased the expression of tyrosine hydroxylase and acetylcholinesterase (AChE, the enzyme that degrades ACh) without affecting enzyme activity but reduced ovarian ACh levels. In vitro exposure of the ovary to NGF (100 ng/ml for 3 h) increased both choline acetyl transferase and vesicular ACh transporter expression in the ovary, with no effect in ACh level. In vivo NGF led to an anovulatory condition with the appearance of follicular cysts and decreased number of corpora lutea (corresponding to noradrenergic activation). To determine whether the predominance of a NE-induced polycystic condition after NGF is responsible for the PCO phenotype, rats were exposed to an intraovarian administration of carbachol (100 μM), a muscarinic cholinergic agonist not degraded by AChE. Decreased the number of follicular cysts and increased the number of corpora lutea, reinforcing that cholinergic activity of the ovary participates in controlling its functions. Although NGF increased the biosynthetic capacity for ACh, it was not available to act in the ovary. Hence, NGF also regulates the ovarian cholinergic system, implying that NGF is the main regulator of the dual autonomic control. These findings highlight the need for research in the treatment of PCO syndrome by modification of locally produced ACh as an in vivo regulator of follicular development.

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Pro-nerve growth factor in the ovary and human granulosa cells

Cited by 7 publications

References 43 publications

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

Human Luteinized Granulosa Cells—A Cellular Model for the Human Corpus Luteum

Nerve Growth Factor: A Dual Activator of Noradrenergic and Cholinergic Systems of the Rat Ovary

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