Wiley Interdisciplinary Reviews : Membrane Transport and Signaling Follow
Subscription journal
ISSN (Online) 2190-4618
Published by John Wiley and Sons
[1594 journals]
Subscription journalISSN (Online) 2190-4618
Published by John Wiley and Sons
[1594 journals]- Issue information
- Targeting endocannabinoid signaling in tumor‐associated macrophages as treatment for glioblastoma multiforme
- Abstract: Glioblastoma multiforme (GBM) is the most common form of primary brain tumor and is diagnosed in approximately 15,000 people each year in the United States alone. No cure for this type of cancer exists, and the current standard of care treatments provide little benefit and are associated with debilitating side effects. Recent evidence shows that a large number of tumor‐associated macrophages (TAMs) invade the GBM tumor mass and secrete factors that directly and indirectly promote tumor growth. TAMs express a panel of unique receptors that could be targeted for therapeutic benefit. One such receptor, cannabinoid receptor 2 (CB2), is a member of the endocannabinoid (eCB) signaling system, and its activation has been shown to tightly control the migration and phenotype of both macrophages and microglia. Additional receptors, also engaged by eCBs and cannabinoid‐like compounds, are expressed by macrophages and microglia. These receptors also control cell migration and phenotype, but exhibit distinct pharmacological profiles and operate through a different mechanism of action. Strong evidence accumulated over the past decade indicates that membrane receptors expressed by TAMs represent novel targeting opportunities to treat GBM tumor progression. Here we review studies that significantly increased our understanding of the molecular mechanism of action of receptors engaged by eCBs and cannabinoid‐like compounds expressed by GBM tumor cells and TAMs. This evidence provides a strong rationale for developing new therapeutics that target the eCB signaling of TAMs for the treatment of GBM while minimizing the typical side effects associated with standard care. WIREs Membr Transp Signal 2014. doi: 10.1002/wmts.101
Conflict of interest: The authors have declared no conflicts of interest for this article.
For further resources related to this article, please visit the WIREs website.
- Abstract: Glioblastoma multiforme (GBM) is the most common form of primary brain tumor and is diagnosed in approximately 15,000 people each year in the United States alone. No cure for this type of cancer exists, and the current standard of care treatments provide little benefit and are associated with debilitating side effects. Recent evidence shows that a large number of tumor‐associated macrophages (TAMs) invade the GBM tumor mass and secrete factors that directly and indirectly promote tumor growth. TAMs express a panel of unique receptors that could be targeted for therapeutic benefit. One such receptor, cannabinoid receptor 2 (CB2), is a member of the endocannabinoid (eCB) signaling system, and its activation has been shown to tightly control the migration and phenotype of both macrophages and microglia. Additional receptors, also engaged by eCBs and cannabinoid‐like compounds, are expressed by macrophages and microglia. These receptors also control cell migration and phenotype, but exhibit distinct pharmacological profiles and operate through a different mechanism of action. Strong evidence accumulated over the past decade indicates that membrane receptors expressed by TAMs represent novel targeting opportunities to treat GBM tumor progression. Here we review studies that significantly increased our understanding of the molecular mechanism of action of receptors engaged by eCBs and cannabinoid‐like compounds expressed by GBM tumor cells and TAMs. This evidence provides a strong rationale for developing new therapeutics that target the eCB signaling of TAMs for the treatment of GBM while minimizing the typical side effects associated with standard care. WIREs Membr Transp Signal 2014. doi: 10.1002/wmts.101
Conflict of interest: The authors have declared no conflicts of interest for this article.
For further resources related to this article, please visit the WIREs website.
- L‐type Ca2+ channels in heart and brain
- Abstract: L‐type calcium channels (Cav1) represent one of the three major classes (Cav1–3) of voltage‐gated calcium channels. They were identified as the target of clinically used calcium channel blockers (CCBs; so‐called calcium antagonists) and were the first class accessible to biochemical characterization. Four of the 10 known α1 subunits (Cav1.1–Cav1.4) form the pore of L‐type calcium channels (LTCCs) and contain the high‐affinity drug‐binding sites for dihydropyridines and other chemical classes of organic CCBs. In essentially all electrically excitable cells one or more of these LTCC isoforms is expressed, and therefore it is not surprising that many body functions including muscle, brain, endocrine, and sensory function depend on proper LTCC activity. Gene knockouts and inherited human diseases have allowed detailed insight into the physiological and pathophysiological role of these channels. Genome‐wide association studies and analysis of human genomes are currently providing even more hints that even small changes of channel expression or activity may be associated with disease, such as psychiatric disease or cardiac arrhythmias. Therefore, it is important to understand the structure–function relationship of LTCC isoforms, their differential contribution to physiological function, as well as their fine‐tuning by modulatory cellular processes. WIREs Membr Transp Signal 2014. doi: 10.1002/wmts.102
Conflict of interest: The authors have declared no conflicts of interest for this article.
For further resources related to this article, please visit the WIREs website.
- Abstract: L‐type calcium channels (Cav1) represent one of the three major classes (Cav1–3) of voltage‐gated calcium channels. They were identified as the target of clinically used calcium channel blockers (CCBs; so‐called calcium antagonists) and were the first class accessible to biochemical characterization. Four of the 10 known α1 subunits (Cav1.1–Cav1.4) form the pore of L‐type calcium channels (LTCCs) and contain the high‐affinity drug‐binding sites for dihydropyridines and other chemical classes of organic CCBs. In essentially all electrically excitable cells one or more of these LTCC isoforms is expressed, and therefore it is not surprising that many body functions including muscle, brain, endocrine, and sensory function depend on proper LTCC activity. Gene knockouts and inherited human diseases have allowed detailed insight into the physiological and pathophysiological role of these channels. Genome‐wide association studies and analysis of human genomes are currently providing even more hints that even small changes of channel expression or activity may be associated with disease, such as psychiatric disease or cardiac arrhythmias. Therefore, it is important to understand the structure–function relationship of LTCC isoforms, their differential contribution to physiological function, as well as their fine‐tuning by modulatory cellular processes. WIREs Membr Transp Signal 2014. doi: 10.1002/wmts.102
Conflict of interest: The authors have declared no conflicts of interest for this article.
For further resources related to this article, please visit the WIREs website.
