Inflammation is associated with progression of actinic keratoses to squamous cell carcinomas in humans

Berhane, Tewelde; Halliday, Gary M.; Cooke, Bridget E.; Barnetson, R S

doi:10.1046/j.1365-2133.2002.04720.x

Cited by 111 publications

(97 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, inflammation and chronic wounds are associated with development of human SCC, as in the development of SCC in burn scars, chronic venous stasis ulcers, and discoid lupus erythematosus (28)(29)(30). Progression of actinic keratosis to SCC has recently also been shown to be associated with an inflammatory stage (31).…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition

Lind

Rozell²,

Wallin³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

107

View full text Add to dashboard Cite

T he Rel͞NF-B transcription factors have a central role in several cellular processes, including proliferation, cell adhesion, apoptosis, and regulation of the immune response (1). Under nonstimulating conditions, NF-B is retained in the cytoplasm in an inactive form because of its interaction with the inhibitory proteins I Bs. In response to an activating stimulus, I B is phosphorylated by an I B kinase (IKK) complex, which targets it for degradation by the proteasome, releasing NF-B, which translocates to the nucleus, where it regulates the transcription of target genes.Evidence gathered from studies during recent years have shown that NF-B has a growth inhibitory function in the skin. Initial studies showed that overexpression of the NF-B subunits p50 or p65 in the basal layer of the murine epidermis by using a keratin 14 (K14) promoter leads to hypoplasia of the epidermis, whereas expression of a superrepressor form of the inhibitor of NF-B type ␣ (I B␣) results in hyperplasia (2). Although K14-I B␣ mice die shortly after birth (day 7), we have shown that mice with keratin 5 (K5)-directed expression of I B␣ (K5-I B␣) to the basal layer of the epidermis survive to adulthood (3). Not only do these mice develop hyperplasia of the epidermis, but the skin phenotype of K5-I B␣ mice is also characterized by an intense neutrophil-dominated inflammation of the skin and an early development of squamous cell carcinomas (SCC).Recent data suggest that human sporadic SCC may show a block in NF-B signaling based on nuclear exclusion of the RelA NF-B subunit (ref. 4 and M.v.H., unpublished results). Furthermore, it was recently shown that coexpression of a superrepressor form of I B␣ and Ha-Ras results in neoplasia resembling invasive SCC in human keratinocytes transplanted to severe combined immunodeficient (scid͞scid) mice, supporting the relevance of a NF-B block in the induction of human SCC (4).Inflammation of the skin with neutrophil infiltration and hyperproliferation is also seen in female heterozygous Ikk␥-deficient mice, which develop a condition similar to the human X-linked disorder Incontinentia Pigmenti (IP) (5, 6). IKK␥ is the regulatory subunit of the IKK complex, which, in addition, contains the two catalytic subunits IKK␣ (IKK1) and IKK␤ (IKK2) (1). It is now well established that human IP results from loss-of-function mutations in the IKK␥ gene (7). Interestingly, subungual keratoacanthoma-like tumors and cases of SCC have been reported as late manifestations of IP (8-11).The catalytic IKK␤ subunit is necessary for activation of NF-B in response to proinflammatory stimuli (1). Skin-specific deletion of the IKK␤ gene, K14-Cre͞Ikk2 FL/FL , was recently shown to result in an inflammatory phenotype with concomitant hyperproliferation of the epidermis (12), very similar to what is seen in the K5-I B␣ mice. Because the K14-Cre͞Ikk2 FL/FL mice die between day 7 and day 9 after birth, it is currently not known whether they, similar to K5-I B␣ mice, are prone to develop SCC.Besides inf lammation and hyperprolifera...

show abstract

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition

Lind

Rozell²,

Wallin³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

107

View full text Add to dashboard Cite

show abstract

“…30,31 Besides, it was observed that the presence of inflamed AKs in humans is associated to the progression to invasive diseases in those lesions. 32 COX-2 and prostaglandin E2 are positive regulators of tumor proliferation, mainly through Ras/Raf/MAPK, and Pt13K/Akt. 33 The MAPK pathway, on the other hand, seems to induce COX-2 production generating a positive feedback cycle.…”

Section: Discussionmentioning

confidence: 99%

Oral acetylsalicylic acid and prevalence of actinic keratosis

Schmitt

Miot

2014

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

show abstract

“…It is also uncertain whether to interpret inflammation of actinic keratosis as a sign of neoplastic progression or regression (22). In any case the severity of the histological grading of the neoplasm is important to consider.…”

Section: Egfr Inhibitors and Inflamed Actinic Keratosis In Perspectivementioning

confidence: 99%

“…Among them, imiquimod and 5-fluorouracil have proven their efficacy (19). Inflammation is typically present during their regression phase (20,21), but also conversely during progression of actinic keratoses to squamous cell carcinomas (22).…”

Section: Actinic Keratoses and Squamous Cell Carcinomasmentioning

confidence: 99%

Erlotinib-responsive actinic keratoses

Hermanns

Pierard²,

Quatresooz³

2007

Oncol Rep

View full text Add to dashboard Cite

Abstract.Erlotinib is an inhibitor of the tyrosine-kinase domain of the epidermal growth factor receptor-1 (EGFR). This drug is used to treat some solid cancers, particularly advanced non-small-cell lung carcinoma. Similar to other EGFR inhibitors, erlotinib is responsible for a series of skin adverse reactions, particularly acneiform lesions. We described the incidental effect of erlotinib on actinic keratoses which became markedly inflamed and showed partial regression. Inflammation appeared to spontaneously decrease while on erlotinib treatment. This reaction in the skin neoplasm is perhaps a visible and accessible model for predicting the effect in the deep-seated neoplasm targeted by the drug.

show abstract

Inflammation is associated with progression of actinic keratoses to squamous cell carcinomas in humans

Abstract: These studies have shown that progression from benign to malignant tumours may be associated with an inflammatory response, which appears to drive malignant conversion, but subsides rapidly following this conversion.

Cited by 111 publications

References 17 publications

Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition

Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition

Oral acetylsalicylic acid and prevalence of actinic keratosis

Erlotinib-responsive actinic keratoses

Contact Info

Product

Resources

About