Ion Channel Targeting with Antibodies and Antibody Fragments for Cancer Diagnosis

Duranti, Claudia; Arcangeli, Annarosa

doi:10.3390/antib8020033

Cited by 24 publications

(17 citation statements)

References 126 publications

(68 reference statements)

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“…Thus, a number of studies are investigating biomarkers for the early onset of the disease or new targets for the best treatment options. Among the many target proteins considered for exploitation with novel therapies are ion channels, which have recently been proposed as appealing druggable markers of the tumorigenic process 2 . This new avenue of oncological application is based on studies describing channels as transport proteins as well as important actors with pore-independent functions in signalling processes.…”

Section: Introductionmentioning

confidence: 99%

Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells

Cojocaru

Şelescu

Domocoş

et al. 2021

Sci Rep

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The transient receptor potential ankyrin type 1 (TRPA1) channel belongs to the TRP superfamily of ion channels. TRPA1 is a membrane protein with multiple functions able to respond to noxious stimuli, reactive oxygen species, inflammatory cytokines or pungent substances, and it participates in pain signalling, taste, inflammation and various steps of the tumorigenic process. To date, no reports have addressed the expression and function of TRPA1 in pancreatic ductal adenocarcinoma (PDAC) cells. This work reports the endogenous expression of TRPA1 channels in human pancreatic adenocarcinoma cell lines and provides insights into the function of the TRPA1 protein in the Panc-1 cell line. This study reports that cell lines isolated from PDAC patients had different levels of TRPA1 expression. The channel activity in Panc-1 cells, as assessed with electrophysiological (whole-cell patch clamp) and microfluorimetry methods, showed that non-selective cationic currents were activated by allyl isothiocyanate (AITC) in Panc-1 cells and inhibited by the selective TRPA1 antagonist A-967079. The current elicited by the specific agonist was associated with a robust increase in intracellular Ca2+. Furthermore, siRNA-induced downregulation of TRPA1 enhanced cell migration in the wound healing assay, indicating a possible role of ion channels independent from pore function. Finally, TRPA1 activation changed the cell cycle progression. Taken together, these results support the idea of channel-dependent and independent role for TRPA1 in tumoral processes.

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Section: Introductionmentioning

confidence: 99%

Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells

Cojocaru

Şelescu

Domocoş

et al. 2021

Sci Rep

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“…However, an increasing number of ion channel protein structures is becoming amenable for in silico drug design (e.g., Brömmel et al (2020b) ). Alternatively, peptide-based blockers or antibody targeting could be more specific alternatives ( Duranti and Arcangeli, 2019 ; Hartung et al, 2020 ; Tajti et al, 2020 ). Here, we list potential target ion channels and the existing knowledge about the consequence of their activation/inhibition in immune, stroma, and tumor cells as well.…”

Section: Therapeutical Approaches and Ion Channels In Pdacmentioning

confidence: 99%

Ion Channels Orchestrate Pancreatic Ductal Adenocarcinoma Progression and Therapy

et al. 2021

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Pancreatic ductal adenocarcinoma is a devastating disease with a dismal prognosis. Therapeutic interventions are largely ineffective. A better understanding of the pathophysiology is required. Ion channels contribute substantially to the “hallmarks of cancer.” Their expression is dysregulated in cancer, and they are “misused” to drive cancer progression, but the underlying mechanisms are unclear. Ion channels are located in the cell membrane at the interface between the intracellular and extracellular space. They sense and modify the tumor microenvironment which in itself is a driver of PDAC aggressiveness. Ion channels detect, for example, locally altered proton and electrolyte concentrations or mechanical stimuli and transduce signals triggered by these microenvironmental cues through association with intracellular signaling cascades. While these concepts have been firmly established for other cancers, evidence has emerged only recently that ion channels are drivers of PDAC aggressiveness. Particularly, they appear to contribute to two of the characteristic PDAC features: the massive fibrosis of the tumor stroma (desmoplasia) and the efficient immune evasion. Our critical review of the literature clearly shows that there is still a remarkable lack of knowledge with respect to the contribution of ion channels to these two typical PDAC properties. Yet, we can draw parallels from ion channel research in other fibrotic and inflammatory diseases. Evidence is accumulating that pancreatic stellate cells express the same “profibrotic” ion channels. Similarly, it is at least in part known which major ion channels are expressed in those innate and adaptive immune cells that populate the PDAC microenvironment. We explore potential therapeutic avenues derived thereof. Since drugs targeting PDAC-relevant ion channels are already in clinical use, we propose to repurpose those in PDAC. The quest for ion channel targets is both motivated and complicated by the fact that some of the relevant channels, for example, KCa3.1, are functionally expressed in the cancer, stroma, and immune cells. Only in vivo studies will reveal which arm of the balance we should put our weights on when developing channel-targeting PDAC therapies. The time is up to explore the efficacy of ion channel targeting in (transgenic) murine PDAC models before launching clinical trials with repurposed drugs.

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“…Hypothetically, good selectivity of IC inactivation and anticancer treatment should lead to immunotherapies based on monoclonal and polyclonal antibodies. However, this strategy is mainly applied for sensitive and selective cancer cell detection, although some use whole antibodies or their fragments directly in cancer therapies has been presented [126]. The application of polyclonal antibodies, targeting 17-amino acid fragments of non-functional ATP-gated receptor P2X 7 , confirmed its therapeutic potential in Phase I of the clinical trial concerning basal cell carcinoma [127].…”

Section: Anticancer Therapies Targeting Ion Channelsmentioning

confidence: 99%

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

et al. 2021

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Modifications of the composition or organization of the cancer cell membrane seem to be a promising targeted therapy. This approach can significantly enhance drug uptake or intensify the response of cancer cells to chemotherapeutics. There are several methods enabling lipid bilayer modifications, e.g., pharmacological, physical, and mechanical. It is crucial to keep in mind the significance of drug resistance phenomenon, ion channel and specific receptor impact, and lipid bilayer organization in planning the cell membrane-targeted treatment. In this review, strategies based on cell membrane modulation or reorganization are presented as an alternative tool for future therapeutic protocols.

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Ion Channel Targeting with Antibodies and Antibody Fragments for Cancer Diagnosis

Cited by 24 publications

References 126 publications

Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells

Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells

Ion Channels Orchestrate Pancreatic Ductal Adenocarcinoma Progression and Therapy

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

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