Iloprost requires the Frizzled-9 receptor to prevent lung cancer

Sompel, Kayla; Dwyer‐Nield, Lori D.; Smith, Alex J.; Elango, Alamelu P.; Backos, Don S.; Zhang, Bicheng; Gross, James; Ternyak, Kristina; Matsuda, Jennifer L.; Kopf, Katrina W; Keith, Robert L.; Tennis, Meredith A.

doi:10.1016/j.isci.2022.104442

Cited by 7 publications

(10 citation statements)

References 35 publications

(67 reference statements)

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“…Iloprost is a lung cancer chemoprevention agent that produces an anti-cancer effect in part by increasing PPAR𝛾 expression and activity and has demonstrated efficacy on bronchial dysplasia in a clinical trial. [11,[47][48][49][50] Curcumin is extracted from the turmeric plant and has anti-inflammatory and growth-suppressive effects in lung cells and mice. [51][52][53] First, hydrogel-embedded PCLS were treated with 10 μm iloprost in culture, and metabolic activity was assessed by Presto Blue analysis on days 0, 3, and 7, to confirm that iloprost did not affect the viability of hydrogel-embedded PCLS.…”

Section: Chemoprevention Agents Acted On Hydrogel-embedded Pclsmentioning

confidence: 99%

Hydrogel‐Embedded Precision‐Cut Lung Slices Model Lung Cancer Premalignancy Ex Vivo

Blomberg,

Sompel,

Hauer

et al. 2023

Adv Healthcare Materials

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Lung cancer is the leading global cause of cancer‐related deaths. Although smoking cessation is the best prevention, 50% of lung cancer diagnoses occur in people who have quit smoking. Research into treatment options for high‐risk patients has been constrained to rodent models, which are time‐consuming, expensive, and require large cohorts. Embedding precision‐cut lung slices (PCLS) within an engineered hydrogel and exposing this tissue to vinyl carbamate, a carcinogen from cigarette smoke, creates an in vitro model of lung cancer premalignancy. Hydrogel formulations are selected to promote early lung cancer cellular phenotypes and extend PCLS viability to six weeks. Hydrogel‐embedded PCLS are exposed to vinyl carbamate, which induces adenocarcinoma in mice. Analysis of proliferation, gene expression, histology, tissue stiffness, and cellular content after six weeks reveal that vinyl carbamate induces premalignant lesions with a mixed adenoma/squamous phenotype. Putative chemoprevention agents diffuse through the hydrogel and induce tissue‐level changes. The design parameters selected using murine tissue are validated with hydrogel‐embedded human PCLS and results show increased proliferation and premalignant lesion gene expression patterns. This tissue‐engineered model of human lung cancer premalignancy is the foundation for more sophisticated ex vivo models that enable study of carcinogenesis and chemoprevention strategies.This article is protected by copyright. All rights reserved

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Section: Chemoprevention Agents Acted On Hydrogel-embedded Pclsmentioning

confidence: 99%

Hydrogel‐Embedded Precision‐Cut Lung Slices Model Lung Cancer Premalignancy Ex Vivo

Blomberg,

Sompel,

Hauer

et al. 2023

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

show abstract

“…Iloprost is a lung cancer chemoprevention agent that produces an anti-cancer effect in part by increasing PPARγ expression and activity and has demonstrated efficacy on bronchial dysplasia in a clinical trial. 11,42,[57][58][59] Curcumin is extracted from the turmeric plant and has anti-inflammatory and growth suppressive effects in lung cells and mice. [60][61][62] First, hydrogel-embedded PCLS were treated with 10 μM iloprost in culture and metabolic activity was assessed by Presto Blue analysis on days 0, 3, and 7, to confirm that iloprost did not affect viability of hydrogel-embedded PCLS.…”

Section: Chemoprevention Agents Acted On Hydrogel-embedded Pclsmentioning

confidence: 99%

Tissue-engineered models of lung cancer premalignancy

Blomberg

Sompel

Hauer

et al. 2023

Preprint

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Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best preventive action, nearly 50% of all lung cancer diagnoses occur in people who have already quit smoking. Research into treatment options for these high-risk patients has been constrained to rodent models of chemical carcinogenesis, which are time-consuming, expensive, and require large numbers of animals. Here we show that embedding precision-cut lung slices within an engineered hydrogel and exposing this tissue to a carcinogen from cigarette smoke creates an in vitro model of lung cancer premalignancy. Hydrogel formulations were selected to promote early lung cancer cellular phenotypes and extend PCLS viability up to six weeks. In this study, hydrogel-embedded lung slices were exposed to the cigarette smoke derived carcinogen vinyl carbamate, which induces adenocarcinoma in mice. At six weeks, analysis of proliferation, gene expression, histology, tissue stiffness, and cellular content revealed that vinyl carbamate induced the formation of premalignant lesions with a mixed adenoma/squamous phenotype. Two putative chemoprevention agents were able to freely diffuse through the hydrogel and induce tissue-level changes. The design parameters selected using murine tissue were validated with hydrogel-embedded human PCLS and results showed increased proliferation and premalignant lesion gene expression patterns. This tissue-engineered model of human lung cancer premalignancy is the starting point for more sophisticated ex vivo models and a foundation for the study of carcinogenesis and chemoprevention strategies.

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“…A single urethane injection leads to an average of 4–6 adenomas in FVB/N and 20–30 in A/J after 14 weeks, which is reduced by intranasal iloprost treatment to an average of 2–3 ( Sompel et al., 2022 ; Tennis et al., 2022 ).…”

Section: Expected Outcomesmentioning

confidence: 99%

“…This protocol diversifies options for chemoprevention studies and offers a relevant and translatable model. For complete details on the use and execution of this protocol, please refer to Sompel et al. (2022) .…”

mentioning

confidence: 99%