The Skin Cancer Paradox of Psoriasis

Nickoloff, Brian J.

doi:10.1001/archderm.140.7.873

Cited by 19 publications

(1 citation statement)

References 19 publications

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“…We demonstrated also that in vivo IGFBP2 is highly expressed in the senescent keratinocyte compartment of psoriatic plaques, which is confined to the upper layers of epidermis and characterized by a strong expression of senescent markers, such as p21 and p16, suggesting its plausible involvement in the biological processes leading to the formation of the psoriatic plaque. In these lesions, keratinocyte senescence reasonably represents a stress response to aberrant cell division and concomitant defective differentiation and is thought to protect psoriatic lesions from tumorigenesis [49]. By contrast, the presence of a robust senescent compartment could be implicated in the perpetuation of the local inflammatory processes typical of psoriasis, through the release of pro-inflammatory mediators, including cytokines, chemokines and extracellular matrix Figure 8.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Insulin-like growth factor binding protein 2 (IGFBP2) contributes to the senescence of keratinocytes in psoriasis by stabilizing cytoplasmic p21

Mercurio

Lulli

Mascia

et al. 2020

Aging

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Psoriasis is an immune-mediated skin disease with a genetic predisposition, characterized by regional expansion and activation of T helper (Th)-1, Th-17, and Th-22 cells, releasing high levels of the pro-inflammatory cytokines IFN-γ, TNF-α, IL-17, and IL-22 in the skin [1, 2]. Epidermal keratinocytes respond to this potent pro-inflammatory environment by hyperproliferating and releasing in turn numerous cytokines and chemokines, responsible for the recruitment and inflammatory auto-amplificatory loop in the skin [3]. In

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Section: Discussionmentioning

confidence: 99%

Intracellular Insulin-like growth factor binding protein 2 (IGFBP2) contributes to the senescence of keratinocytes in psoriasis by stabilizing cytoplasmic p21

Mercurio

Lulli

Mascia

et al. 2020

Aging

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Role of TGFβ in skin inflammation and carcinogenesis

Han

et al. 2006

Molecular Carcinogenesis

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The functions of transforming growth factor beta-1(TGFbeta1) are cell-context specific. We have found that TGFbeta1 expression in human skin squamous cell carcinoma (SCC) samples has two distinct distribution patterns: (1) either predominantly in suprabasal layers or (2) throughout tumor epithelia including basal proliferative cells. To understand whether the spatial TGFbeta1 expression patterns affect its functions, we have generated several keratinocyte-specific transgenic mouse models in which TGFbeta1 overexpression can be induced either predominantly in the suprabasal epidermis or in the basal layer of the epidermis and hair follicles. Suprabasal TGFbeta1 overexpression inhibits keratinocyte proliferation, suppresses skin carcinogenesis at early stages, but promotes tumor invasion at later stages. In contrast, TGFbeta1 overexpression in the basal layer of the epidermis and hair follicles causes a severe inflammatory skin disorder and epidermal hyperproliferation. Given the importance of inflammation in cancer development, our data suggest that TGFbeta1-induced skin inflammation may override its tumor suppressive effect at early stages during skin carcinogenesis. This hypothesis is further suggested by our recent study that Smad3 knockout mice are resistant to skin chemical carcinogenesis at least in part via abrogation of endogenous TGFbeta1-induced inflammation. This review intends to summarize current insights into the role of TGFbeta1 in skin inflammation and carcinogenesis.

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Imiquimod attenuates the growth of UVB‐Induced SCC in mice through Th1/Th17 cells

Yokogawa

Takaishi

Nakajima

et al. 2012

Molecular Carcinogenesis

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Imiquimod (IMQ), a Toll-like receptor (TLR) 7/8 agonist, has been used to treat various skin neoplasms, including genital warts, actinic keratoses and superficial basal cell carcinomas. Although IMQ has been recognized to activate both innate and adaptive immunity, the underlying mechanism(s) by which IMQ exerts its anti-tumor activity in vivo remains largely unknown. In this study, we took advantage of skin cancer-prone mice to characterize the effects of IMQ on ultraviolet irradiation (UV)-induced de novo carcinogenesis. Transgenic mice with keratinocytes expressing constitutively activated Stat3 (K5.Stat3C mice) developed squamous cell carcinomas (SCC in situ) as early as after 14 weeks of UVB irradiation, while wild-type mice required much higher doses of UVB with more than 25 weeks of UVB irradiation to produce SCC. Topical treatment of K5.Stat3C mice with IMQ attenuated UVB-induced epidermal dysplasia (SCC in situ). In addition, SCC growth due to increased total irradiation doses was significantly attenuated by IMQ treatment. Topical IMQ treatment induced T cell and plasmacytoid dendritic cell infiltrates at the tumor sites, where levels of IL-12/23p40, IL-12p35, IL-23p19, IL-17A and IFN-γ mRNAs were up-regulated. Immunohistochemistry revealed T cell infiltrates consisting of T1, Th17 and CD8+ T cells. We speculate that topical IMQ treatment attenuates the de novo growth of UVB-induced SCC through activation of Th17/Th1 cells and cytotoxic T lymphocytes.

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The Skin Cancer Paradox of Psoriasis

Cited by 19 publications

References 19 publications

Intracellular Insulin-like growth factor binding protein 2 (IGFBP2) contributes to the senescence of keratinocytes in psoriasis by stabilizing cytoplasmic p21

Intracellular Insulin-like growth factor binding protein 2 (IGFBP2) contributes to the senescence of keratinocytes in psoriasis by stabilizing cytoplasmic p21

Role of TGFβ in skin inflammation and carcinogenesis

Imiquimod attenuates the growth of UVB‐Induced SCC in mice through Th1/Th17 cells

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