Metastasis requires cancer cells to undergo poorly-understood metabolic changes [1][2][3] . We found that metabolic differences among melanoma cells confer differences in metastatic potential as a result of differences in Monocarboxylate Transporter 1 (MCT1) function. In vivo isotope tracing in patient-derived xenografts revealed differences in nutrient handling between efficiently and inefficiently metastasizing melanomas, with circulating lactate being a more prominent source of tumor lactate in efficient metastasizers. Efficient metastasizers had higher MCT1 levels and MCT1 inhibition reduced lactate uptake. MCT1 inhibition had little effect on primary subcutaneous tumor growth but depleted circulating melanoma cells and reduced metastatic disease burden in patientderived xenografts and in mouse melanomas. MCT1 inhibition suppressed the oxidative pentose phosphate pathway and increased ROS levels. Anti-oxidants blocked the effect of MCT1 inhibition on metastasis. MCT1 high and MCT1 −/low cells from the same melanomas had similar Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Proliferating cells depend on glucose uptake more than quiescent cells for their growth. While glucose transport in keratinocytes is mediated largely by the Glut1 facilitative transporter, the keratinocyte-specific ablation of Glut1 did not compromise mouse skin development and homeostasis. Ex vivo metabolic profiling revealed altered sphingolipid, hexose, amino acid, and nucleotide metabolism in Glut1-deficient keratinocytes, suggesting metabolic adaptation. On the other hand, Glut1-deficient keratinocytes in culture displayed metabolic and oxidative stress and impaired proliferation. Similarly, Glut1 deficiency impaired in vivo keratinocyte proliferation and migration within wounded or UV-damaged mouse skin. Notably, both genetic and pharmacological Glut1 inactivation reduced hyperplasia in mouse models of psoriasis-like disease. Topical application of a Glut1 inhibitor also reduced inflammation in these models. Glut1 inhibition decreased expression of pathology-associated genes in human psoriatic skin organoids. Thus, Glut1 is selectively required for injury- and inflammation-associated keratinocyte proliferation, and its inhibition offers a novel treatment strategy for psoriasis.
Background/purpose: Atopic dermatitis (AD) is a common and extremely burdensome skin disorder with limited therapeutic options. Ultraviolet (UV) phototherapy is a well tolerated, efficacious treatment for AD, but its use is limited by a lack of guidelines in the optimal choice of modality and dosing. Given this deficit, we aim to develop suggestions for the treatment of AD with phototherapy by systematically reviewing the current medical literature. Methods: Data sources: All data sources were identified through searches of MEDLINE via the Ovid interface, the Cochrane Central Register of Controlled Trials, and a complementary manual literature search. Study selection: Studies selected for review met these inclusion criteria, as applied by multiple reviewers: controlled clinical trials of UV phototherapy in the management of AD in human subjects as reported in the English-language literature. Studies limited to hand dermatitis and studies in which subjects were allowed unmonitored use of topical corticosteroids or immunomodulators were excluded. Data extraction: Included studies were assessed by multiple independent observers who extracted and
Background Human Polyomavirus 6 (HPyV6) and Human Polyomavirus 7 (HPyV7) are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. Objective We determined whether biopsies showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. Methods We screened biopsies showing “peacock plumage” histology by PCR for human polyomaviruses. Cases positive for HPyV 6 or 7 were then analyzed by immunohistochemistry, electron microscopy (EM), immunofluorescence, quantitative PCR, and complete sequencing, including unbiased, next generation sequencing (NGS). Results We identified three additional cases of HPyV6 or 7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared to normal skin and the identification of intact virions by both EM and NGS support a role for active viral infections in these skin diseases. Limitation This was a small case-series of archived materials. Conclusion We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a unique histologic pattern and describe this entity as “HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatosis (H6PD and H7PD).”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.