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Romanian Journal of Morphology and... 2021Keratoacanthoma (KA) is an epithelial tumor of the skin, classically considered as having a malignant transformation risk of 15%; however, many authors and the new World...
Keratoacanthoma (KA) is an epithelial tumor of the skin, classically considered as having a malignant transformation risk of 15%; however, many authors and the new World Health Organization (WHO) Classification of skin tumors consider KA as an incipient variant of the cutaneous squamous cell carcinoma (SCC). The aims of the study were to assess the clinical, histopathological (HP) and immunohistochemical (IHC) aspects of the KA and the role of these factors in malignancy occurrence. The studied group comprises 194 patients diagnosed with KA or malignant KA, hospitalized in the Clinic of Dermatology, Emergency County Hospital, Craiova, Romania, between 2006 and 2019. There were 83 males and 111 females, aged 34 to 90 years, 57.21% of the patients being from the rural environment. The histopathology diagnosed 51 KAs and 143 malignant KAs (SCCs). Clinical diagnosis had a limited value in detecting the absence or presence of malignancy in the KA lesion, due to a low accuracy (36.08% and 29.89%, respectively) and specificity (23.07% and 27.02%, respectively); therefore, the HP exam of the surgical excision specimen has a paramount importance in establishing the diagnosis. IHC analysis revealed that the immunostainings for apoptosis-associated proteins and keratinocyte proliferative activity [p53, B-cell lymphoma-2 (Bcl-2), Ki-67 and proliferating cell nuclear antigen (PCNA)] provide some arguments to differentiate between KA and SCC in the studied cases. The correlation of clinical, HP and IHC data lead to an accurate diagnosis of KA; moreover, the clinical, HP and IHC data sustain the idea that KA is a particular form of well-differentiated SCC, which require an active therapeutic attitude.
Topics: Carcinoma, Squamous Cell; Cell Proliferation; Female; Humans; Keratoacanthoma; Male; Skin; Skin Neoplasms
PubMed: 35024732
DOI: 10.47162/RJME.62.2.10 -
Skin Pharmacology and Physiology 2020Skin cancer is the most common cancer worldwide, with rapidly increasing incidence and consistent mortality. Skin cancer encompasses melanoma and non-melanoma skin... (Review)
Review
Skin cancer is the most common cancer worldwide, with rapidly increasing incidence and consistent mortality. Skin cancer encompasses melanoma and non-melanoma skin cancer, which in turn is mainly divided into cutaneous squamous cell carcinoma and basal cell carcinoma. Small noncoding micro-RNAs (miRNAs) regulate protein expression after transcription and play a role in the development and progression of skin cancer. Deregulated expression of miRNAs in skin cancer is associated with cell proliferation, angiogenesis, metastasis, apoptosis, immune response, and drug resistance. Specific patterns of miRNAs in specific skin cancer types can be used as diagnostic markers. For therapeutic purposes, both miRNA and chemically modified variants thereof as well as miRNA antagonists (antagomiRs) or RNA inhibitors may be applied topically. Due to their specific physicochemical properties, physical or chemical diffusion promoters are used with varying degrees of success. There is no question by now that such preparations have a high potential for the treatment of epithelial skin tumors in particular.
Topics: Administration, Topical; Animals; Drug Carriers; Drug Delivery Systems; Electroporation; Humans; MicroRNAs; Skin; Skin Neoplasms
PubMed: 33080592
DOI: 10.1159/000509879 -
European Journal of Immunology Jul 2021Mononuclear phagocytes consisting of monocytes, macrophages, and DCs play a complex role in tumor development by either promoting or restricting tumor growth. Cutaneous...
Mononuclear phagocytes consisting of monocytes, macrophages, and DCs play a complex role in tumor development by either promoting or restricting tumor growth. Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer arising from transformed epidermal keratinocytes. While present at high numbers, the role of tumor-infiltrating and resident myeloid cells in the formation of cSCC is largely unknown. Using transgenic mice and depleting antibodies to eliminate specific myeloid cell types in the skin, we investigated the involvement of mononuclear phagocytes in the development of UV-induced cSCC in K14-HPV8-E6 transgenic mice. Although resident Langerhans cells were enriched in the tumor, their contribution to tumor formation was negligible. Equally, dermal macrophages were dispensable for the development of cSCC. In contrast, mice lacking circulating monocytes were completely resistant to UV-induced cSCC, indicating that monocytes promote tumor development. Collectively, these results demonstrate a critical role for classical monocytes in the initiation of skin cancer.
Topics: Animals; Carcinogenesis; Carcinoma, Squamous Cell; Cell Line, Tumor; Epidermis; Female; Keratinocytes; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Monocytes; Skin; Skin Neoplasms; Ultraviolet Rays
PubMed: 33759186
DOI: 10.1002/eji.202048841 -
Frontiers in Public Health 2021Ultraviolet radiation (UVR) is a known carcinogen participated for the development of skin cancers. Solar UVR exposure, particularly ultraviolet B (UVB), is the mostly... (Review)
Review
Ultraviolet radiation (UVR) is a known carcinogen participated for the development of skin cancers. Solar UVR exposure, particularly ultraviolet B (UVB), is the mostly significant environmental risk factor for the occurrence and progress of basal cell carcinoma(BCC). Both cumulative and intermittent high-grade UVR exposure could promote the uncontrolled replication of skin cells. There are also exsiting other contributing environmental factors that combine with the UVR exposure to promote the development of BCC. DNA damage in formation of skin cancers is considered to be a result of UVR toxicity. It is UVR that could activate a series of oncogenes simultaneously inactivating tumor suppressor genes and aberrant proliferation and survival of keratinocytes that repair these damages. Furthermore, mounting evidence demonstrates that inflammatory responses of immune cells in the tumor microenvironment plays crucial role in the skin tumorigenesis as well. In this chapter, we will follow the function of UVR in the onset and development of BCC. We describe the factors that influence BCC induced by UVR, and also review the recent advances of pathogenesis of BCC induced by UVR from the genetic and inflammatory aspects.
Topics: Carcinoma, Basal Cell; Humans; Skin; Skin Neoplasms; Sunlight; Tumor Microenvironment; Ultraviolet Rays
PubMed: 34368047
DOI: 10.3389/fpubh.2021.666528 -
Experimental Dermatology Nov 2022Interleukin (IL)-38 is a member of the IL-1 cytokine family with reported anti-inflammatory activity. The highest constitutive IL-38 expression is detected in the skin,...
Interleukin (IL)-38 is a member of the IL-1 cytokine family with reported anti-inflammatory activity. The highest constitutive IL-38 expression is detected in the skin, where it is mainly produced by differentiating keratinocytes. However, little data are available regarding its biological functions. In this study, we investigated the role of IL-38 in skin physiology. We demonstrate here that dermal fibroblasts and epithelial cells of skin appendages, such as eccrine sweat glands and sebaceous glands, also express IL-38. Next, using two- and three-dimensional cell cultures, we show that endogenous expression of IL-38 correlates with keratinocyte differentiation and its ectopic overexpression inhibits keratinocyte proliferation and enhances differentiation. Accordingly, immunohistochemical analysis revealed downregulation of IL-38 in skin pathologies characterized by keratinocyte hyperproliferation, such as psoriasis and basal or squamous cell carcinoma. Finally, intracellular IL-38 can shuttle between the nucleus and the cytoplasm and its overexpression modulates the activity of the transcription regulators YAP and ID1. Our results indicate that IL-38 can act independently from immune system activation and suggest that it may affect the epidermis directly by decreasing proliferation and promoting differentiation of keratinocytes. These data suggest an important role of keratinocyte-derived IL-38 in skin homeostasis and pathologies characterized by epidermal alterations.
Topics: Humans; Keratinocytes; Epidermis; Skin; Epidermal Cells; Psoriasis; Cell Differentiation; Cell Proliferation; Interleukins
PubMed: 35833307
DOI: 10.1111/exd.14644 -
Experimental Dermatology Feb 2020Caveolae are flask-shaped invaginations of the cell membrane rich in cholesterol and sphingomyelin, with caveolin proteins acting as their primary structural components... (Review)
Review
Caveolae are flask-shaped invaginations of the cell membrane rich in cholesterol and sphingomyelin, with caveolin proteins acting as their primary structural components that allow compartmentalization and orchestration of various signalling molecules. In this review, we discuss how pleiotropic functions of caveolin-1 (Cav1) and its intricate roles in numerous cellular functions including lipid trafficking, signalling, cell migration and proliferation, as well as cellular senescence, infection and inflammation, are integral for normal development and functioning of skin and its appendages. We then examine how disruption of the homeostatic levels of Cav1 can lead to development of various cutaneous pathophysiologies including skin cancers, cutaneous fibroses, psoriasis, alopecia, age-related changes in skin and aberrant wound healing and propose how levels of Cav1 may have theragnostic value in skin physiology/pathophysiology.
Topics: Bacterial Infections; Caveolae; Caveolin 1; Cell Movement; Cell Proliferation; Cellular Senescence; Fibrosis; Hair; Humans; Inflammation; Lipid Metabolism; Psoriasis; Signal Transduction; Skin; Skin Neoplasms; Skin Physiological Phenomena; Wound Healing
PubMed: 31845391
DOI: 10.1111/exd.14068 -
Journal of Experimental & Clinical... Aug 2022Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated...
BACKGROUND
Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear.
METHODS
Epidermal CD147-overexpression or knockout (Epi or Epi) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation.
RESULTS
We found that specific overexpression of CD147 in the epidermis (Epi) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in Epi transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in Epi transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of CD147. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs.
CONCLUSION
Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway.
Topics: Animals; Basigin; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Epidermis; Mice; Ribosomal Protein S6 Kinases, 90-kDa; Skin Neoplasms; Transcription Factor AP-1
PubMed: 35964097
DOI: 10.1186/s13046-022-02427-w -
Journal of Cutaneous Pathology Dec 2021NUT carcinomas are genetically defined epithelial neoplasms. Most tumors harbor fusions of NUTM1 with BRD4 or BRD3. Their histopathologic features have been...
NUT carcinomas are genetically defined epithelial neoplasms. Most tumors harbor fusions of NUTM1 with BRD4 or BRD3. Their histopathologic features have been predominantly reported as undifferentiated or poorly differentiated squamous cell carcinoma, and clinically they tend to be aggressive cancers. However, recent studies have revealed a broader spectrum of NUTM1-rearranged neoplasms with several new fusion partners and associated variable histopathologic phenotypes and clinical behaviors, including benign and malignant cutaneous poroid tumors. We report herein a primary invasive carcinoma of skin adnexal origin with a previously undescribed fusion between BRD3 and NUTM2B. The tumor occurred on the shoulder of a 7-year-old girl and was excised with negative margins. A sentinel lymph node was positive. After follow-up of 23 months, and without systemic treatment, the child remains free of tumor. This case expands the spectrum of NUT carcinomas by including a skin adnexal variant with follicular infundibular differentiation, a novel genomic aberration, and preliminary evidence of a less aggressive clinical course.
Topics: Carcinoma, Skin Appendage; Child; Female; Humans; Neoplasm Proteins; Oncogene Proteins, Fusion; Skin Neoplasms; Transcription Factors
PubMed: 34296453
DOI: 10.1111/cup.14107 -
Advances in Experimental Medicine and... 2023Bioengineered in vitro three-dimensional (3D) skin model has emerged as a promising tool for recapitulating different types of skin cancer and performing pre-clinical...
Bioengineered in vitro three-dimensional (3D) skin model has emerged as a promising tool for recapitulating different types of skin cancer and performing pre-clinical tests. However, a full-thickness 3D model including the epidermis, dermis, and hypodermis layers is scarce despite its significance in human physiology and diverse biological processes. In this book chapter, an attempt has been made to summarize various skin cancer models, including utilized skin layers, materials, cell lines, specific treatments, and fabrication techniques for three types of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Subsequently, current limitations and future directions of skin cancer models are discussed. The knowledge of the current status of skin cancer models can provide various potential applications in cancer research and thus a more effective way for cancer treatment.
Topics: Humans; Tissue Engineering; Skin Neoplasms; Carcinoma, Basal Cell; Skin; Melanoma
PubMed: 36484897
DOI: 10.1007/5584_2022_755 -
The Journal of Investigative Dermatology Apr 2021This Perspective briefly reviews the relationship between UV-induced mutations in habitually sun-exposed human skin and subsequent development of actinic keratoses (AKs)... (Review)
Review
This Perspective briefly reviews the relationship between UV-induced mutations in habitually sun-exposed human skin and subsequent development of actinic keratoses (AKs) and skin cancers. It argues that field therapy rather than AK-selective therapy is the more logical approach to cancer prevention and hypothesizes that treatment early in the process of field cancerization, even prior to the appearance of AKs, may be more effective in preventing cancer as well as more beneficial for and better tolerated by at-risk individuals. Finally, the Perspective encourages use of rapidly advancing DNA analysis techniques to quantify mutational burden in sun-damaged skin and its reduction by various therapies.
Topics: Administration, Cutaneous; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Chemexfoliation; Combined Modality Therapy; Cryosurgery; Curettage; DNA Damage; DNA Mutational Analysis; Dermatology; Disease Progression; Electrocoagulation; Fluorouracil; Humans; Keratinocytes; Keratosis, Actinic; Mutation; Photochemotherapy; Skin; Skin Neoplasms; Sunscreening Agents; Ultraviolet Rays
PubMed: 32956650
DOI: 10.1016/j.jid.2020.09.002