Interleukin-1α leads to growth hormone deficiency in adamantinomatous craniopharyngioma by targeting pericytes: implication in pituitary fibrosis

Mao, Jian; Qiu, Binghui; Mei, Fen; Liu, Fan; Feng, Zhanpeng; Fan, Jia; Nie, Jing; Huang, Lijun; Liao, Xixian; Wang, Zhenhao; Zeng, Jiahui; Weng, Zelin; Zang, Nailiang; Qi, Songtao; Bao, Yun

doi:10.1016/j.metabol.2019.153998

Cited by 10 publications

(7 citation statements)

References 37 publications

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“…Of various inflammatory factors regulated by IGF1R, IL-6 can promote process of the epithelial-mesenchymal transformation (EMT) in ACP [18]. IL-1 can act on peri-pituitary cells to promote fibrosis [25], suggesting that targeting IGF1R might not only inhibit tumor proliferation but also exert an anti-tumor effect by controlling inflammation. IL-6 promotes EMT of the tumor.…”

Section: Discussionmentioning

confidence: 99%

Expression of Insulin-Like Growth Factor Type 1 Receptor Is Linked to Inflammation in Adamantinomatous Craniopharyngioma

Yang

et al. 2021

Neuroendocrinology

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Introduction Insulin-like growth factor type 1 receptor (IGF1R) is overexpressed in various malignant tumors, which relates to their transformation and recurrence. Craniopharyngioma is a benign tumor with malignant results, often accompanied by a severe inflammatory reaction. However, the relationship between IGF1R expression and the inflammatory response of craniopharyngioma is unclear. Methods We enrolled 85 patients with adamantinomatous craniopharyngioma (ACP) in a study to explore the relationship between IGF1R expression and clinical features of this disease. Results Patients in the IGF1R high expression group had a significantly higher incidence of hypopituitarism, higher recurrence rate and lower progression-free survival. Beta-catenin can further regulate expression of the stem cell marker, CD44, by regulating IGF1R. Using immunofluorescence, we found that tumor stem cell–like cells did not express phosphorylated (p)-ERK, although p-ERK activation was evident in the surrounding cells. Picropodophyllin, a specific inhibitor of IGF1R, increased the expression of p-ERK protein, and decreased the transcription level of interleukin-6. Conclusions High expression of IGF1R might promote inflammation of ACP, which might be an unfavorable factor for pituitary function and prognosis. The high expression of IGF1R in tumor cell stem-like cells might inhibit the expression of p-ERK and promote the generation of inflammatory factors. Insulin-like growth factor type 1 receptor plays a stemness maintenance role in ACP and regulates the production of inflammatory factors through a p-ERK pathway, which suggests that targeting IGF1R and p-ERK might provide a new direction for alleviating tumor inflammation.

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Section: Discussionmentioning

confidence: 99%

Expression of Insulin-Like Growth Factor Type 1 Receptor Is Linked to Inflammation in Adamantinomatous Craniopharyngioma

Yang

et al. 2021

Neuroendocrinology

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“…Since IL-1β is a potent stimulator of aromatase activity and of subsequent estrogen synthesis [43], we hereby hypothesize that placental IL-1β production is increased in ET sows in an attempt to counteract the lack of estrogen signaling from the non-rejected allogeneic embryos remaining in utero. Moreover, allogeneic placentae also showed a higher expression of IL-1α compared to C+ conceptuses at D24 of pregnancy, which has been shown to negatively impact cell growth [45], suggesting that the development of the allogeneic embryos may be delayed in comparison with hemi-allogeneic conceptuses. This fact evidently agrees with the morphological findings among the conceptuses analyzed after collection at D24 of pregnancy, whereas the hemi-allogeneic conceptuses were in a more advanced stage of development when compared to allogeneic; both the healthy conceptuses and the delayed counterparts.…”

Section: Discussionmentioning

confidence: 99%

Pig Pregnancies after Transfer of Allogeneic Embryos Show a Dysregulated Endometrial/Placental Cytokine Balance: A Novel Clue for Embryo Death?

et al. 2020

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Pig embryo transfer (ET) is burdened by high embryo mortality, with cytokines playing a significant role in recruitment of immune cells during embryo attachment and placentation. We hereby tested if their levels in endometrium and placenta from sows carrying hemi-allogeneic (artificially inseminated sows; C+ positive control) or allogeneic embryos (sows subjected to ET; ET) during peri-implantation (D18) or post-implantation (D24) are suitable mirrors of embryo rejection or tolerance after ET. Non-pregnant sows (C−) were used as negative controls. A set of cytokines was assayed in the tissues through multiplexed microsphere-based flow cytometry (Luminex xMAP, Millipore. USA). Fewer (58.7%. p < 0.003) conceptuses were recovered at D24 after ET compared to C+ (80.9%); with more than 20% of the ET conceptuses being developmentally delayed. Cytokine levels shifted during implantation. Anti-inflammatory IL-10 levels were significantly (p < 0.05) lower in ET sows compared to C+ at D24 of pregnancy. The C+ controls (carrying hemi-allogeneic embryos) consistently showed higher levels of pro-inflammatory TNF-α, IFN-γ, and IL-2 cytokines at D18 and IL-1α at D24, compared to the ET group. This clear dysregulation of pro- and anti-inflammatory cytokine levels in sows subjected to ET could be associated with an impaired maternal immune tolerance, explaining the high embryonic mortality of ET programs.

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“…Inflammation-related cross-talk between aCP cells and pericytes in the pituitary could be an essential factor in the formation of GH deficiency through IL-1α-induced pituitary fibrosis. Neutralization of IL-1α signaling might be a potential therapy for GH deficiency in aCP [46].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Endocrine and Metabolic Comorbidities in a National Cohort of Patients with Craniopharyngioma

et al. 2020

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Objective: The major part of craniopharyngioma (CP) morbidity is the tumor and/or treatment-related damage, which results in impaired function of the hypothalamic-pituitary axes and metabolic derangements. The aim of the study was to analyze the prevalence of long-term endocrine and metabolic comorbidities in a national cohort of CP patients based on the age at diagnosis and histology criteria. Design: A retrospective-prospective longitudinal cohort analysis. Methods: Forty-six patients with CP treated from 1979 onwards (19 with childhood-onset disease) in a single university institution were included in our study. Median follow-up from presentation was 12.8 years (interquartile range: 8.3-22.2 years) and comparable between age-at-diagnosis and histological subtype groups. Data on tumor histology were extracted from patients' records and re-evaluated if tissue samples were available (n = 32). Results: Childhood-onset patients presented more frequently with headache, and adult-onset with visual impairment. Prevalence of at least one pituitary axis affected increased from 54% at presentation to 100% at follow-up in childhood-onset and from 41 to 93% in adult-onset CP. Growth hormone deficiency, central diabetes insipidus, and panhypopituitarism were more prevalent in childhood-onset adamantinomatous CP (aCP) and least prevalent in adult-onset papillary CP (pCP). At followup, metabolic syndrome (MetS) was diagnosed in 80% of childhood-onset and 68% of adult-onset patients (p = 0.411). In the latter group, it tended to be more frequent in the aCP than pCP subtype (80 vs. 50%, p = 0.110). Conclusions: Long-Long-Term Outcomes in Craniopharyngioma 47 Horm Res Paediatr 2020;93:46-57 term endocrine and metabolic complications are very frequent in childhood-and adult-onset CP patients of both histological subtypes. The prevalence of MetS was higher compared to the largest cohort previously reported.

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Interleukin-1α leads to growth hormone deficiency in adamantinomatous craniopharyngioma by targeting pericytes: implication in pituitary fibrosis

Cited by 10 publications

References 37 publications

Expression of Insulin-Like Growth Factor Type 1 Receptor Is Linked to Inflammation in Adamantinomatous Craniopharyngioma

Expression of Insulin-Like Growth Factor Type 1 Receptor Is Linked to Inflammation in Adamantinomatous Craniopharyngioma

Pig Pregnancies after Transfer of Allogeneic Embryos Show a Dysregulated Endometrial/Placental Cytokine Balance: A Novel Clue for Embryo Death?

Prevalence of Endocrine and Metabolic Comorbidities in a National Cohort of Patients with Craniopharyngioma

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