CD200 Upregulation in Vascular Endothelium Surrounding Cutaneous Squamous Cell Carcinoma

Belkin, Daniel A.; Mitsui, Hiroshi; Wang, Claire Q.F.; Gonzalez, Juana; Zhang, Shali; Shah, Kejal R.; Coats, Israel; Suárez‐Fariñas, Mayte; Krueger, James G.; Felsen, Diane; Carucci, John A.

doi:10.1001/jamadermatol.2013.1609

Cited by 35 publications

(34 citation statements)

References 42 publications

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“…Th2 cells and macrophages as well as melanocytes produce IL-24 (Poindexter et al , 2005), and those cells reside in the SCC microenvironment. In fact, IL-24 mRNA was also up-regulated in inflammatory infiltrating cell regions surrounding tumor nests compared to normal reticular dermis (Belkin et al , 2013). We thus concluded that IL-24 can be derived from multiple cell types including cancer cells within the SCC microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of the Leading Edge of Cutaneous Squamous Cell Carcinoma: IL-24-Driven MMP-7

Mitsui

Suárez‐Fariñas

Gulati

et al. 2014

Journal of Investigative Dermatology

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The precise mechanisms governing invasion at the leading edge of SCC and its subsequent metastasis are not fully understood. We aimed to define the cancer related molecular changes that distinguish non-invasive tumor from invasive SCC. To this end, we combined laser capture microdissection with cDNA microarray analysis. We defined invasion-associated genes as those differentially regulated only in invasive SCC nests, but not in actinic keratosis or in situ SCC, compared to normal epidermis. There were 383 up- and 354 down-regulated genes in the “invasion set.” SCC invasion was characterized by aberrant expression of various proteolytic molecules. We noted increased expression of MMP7 and IL-24 in invasive SCC. IL-24 induced the expression of MMP7 in SCC cells in culture. In addition, blocking of MMP7 by a specific antibody significantly delayed the migration of SCC cells in culture. These results suggest a possible contribution of IL-24 to SCC invasion via enhancing focal expression of MMP7, though IL-24 has been suggested to have anti-tumor growth effects in other cancer types. Identification of regional molecular changes that regulate cancer invasion may facilitate the development of new targeted treatments for aggressive cancer.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of the Leading Edge of Cutaneous Squamous Cell Carcinoma: IL-24-Driven MMP-7

Mitsui

Suárez‐Fariñas

Gulati

et al. 2014

Journal of Investigative Dermatology

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“…CD200 gene and message were upregulated in SCC stroma (Belkin et al, 2013). E2F1 and E2F7 were both found overexpressed in cSCCs compared with normal epidermis (Belkin et al, 2013). With detection by quantitative real-time reverse transcriptase polymerase chain reaction, DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were found significantly higher in the SCC than the healthy controls .…”

Section: Abnormally Expressed Genes In Csccmentioning

confidence: 90%

“…While the normal epidermis showed a negative to weak-positive expression of MUC4, its expression was significantly upregulated in SCCs where the intensity of staining correlated negatively with tumour grade and positively with age (Chakraborty et al, 2010). CD200 gene and message were upregulated in SCC stroma (Belkin et al, 2013). E2F1 and E2F7 were both found overexpressed in cSCCs compared with normal epidermis (Belkin et al, 2013).…”

Section: Abnormally Expressed Genes In Csccmentioning

confidence: 95%

Systematical Analysis of Cutaneous Squamous Cell Carcinoma Network of microRNAs, Transcription Factors, and Target and Host Genes

Wang

Xu²,

Wang³

2015

Asian Pacific Journal of Cancer Prevention

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Background: MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signal control networks. Materials and Methods: Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs, and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context of the regulation and significant patterns were extracted. Results: Participants of the networks were evaluated based on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2, as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Up or down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13, were in line with expectation while others, including FGFR3, need further investigation of their unexpected behavior. Conclusions: The present research suggests that dozens of components, miRNAs, TFs, target genes and host genes included, unite as networks through their regulation to function systematically in human cSCC. Networks built under the currently available sources provide critical signal controlling pathways and frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

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“…HDBECs (PromoCell, Heidelberg, Germany) were cultured as previously described [27]. HDBECs were transfected using PromoFectin-HUVEC according to manufactures recommendations.…”

Section: Methodsmentioning

confidence: 99%

CARD14 Expression in Dermal Endothelial Cells in Psoriasis

et al. 2014

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Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31+ endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14+ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14+ CD31+ ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin.

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CD200 Upregulation in Vascular Endothelium Surrounding Cutaneous Squamous Cell Carcinoma

Abstract: CD200 expression on local blood vessels may promote tumor progression by suppressing CD200R myeloid cells during diapedesis. These data highlight a previously unrecognized mechanism of immune evasion by SCC and may provide guidance for the development of targeted therapy.

Cited by 35 publications

References 42 publications

Gene Expression Profiling of the Leading Edge of Cutaneous Squamous Cell Carcinoma: IL-24-Driven MMP-7

Gene Expression Profiling of the Leading Edge of Cutaneous Squamous Cell Carcinoma: IL-24-Driven MMP-7

Systematical Analysis of Cutaneous Squamous Cell Carcinoma Network of microRNAs, Transcription Factors, and Target and Host Genes

CARD14 Expression in Dermal Endothelial Cells in Psoriasis

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