Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV

Narducci, Maria Grazia; Scala, Enrico; Bresin, Antonella; Caprini, Elisabetta; Picchio, Maria; Remotti, Daniele; Ragone, Gianluca; Nasorri, Francesca; Frontani, Marina; Arcelli, Diego; Volinia, Stefano; Lombardo, Giuseppe; Baliva, Giannandrea; Napolitano, Monica; Russo, Giandomenico

doi:10.1182/blood-2005-04-1492

Cited by 153 publications

(143 citation statements)

References 62 publications

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“…As model cell lines, we choose the human CTCL cell lines Hut78, SeAx, and MyLa. The cell lines responded to CCL18 in an in vitro chemotaxis assay, but the response was weak compared with CXCL12, a chemokine abundantly expressed in CTCL skin lesions 23 ( Figure 6A). Therefore, induction of tumor cell migration might not be a main function of CCL18 in CTCL.…”

Section: Functional Impact Of Ccl18 On Ctcl Cell Linesmentioning

confidence: 99%

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

Günther

Zimmermann

Berndt

et al. 2011

The American Journal of Pathology

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Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma (CTCL), which can deteriorate from patch stage to dermal-based tumors and systemic involvement in years. The interaction of chemokines in the skin with CTCL cells might have implications for the pathogenesis of the disease. In this study, we show by PCR analysis and immunofluorescence staining that the chemokine CCL18 is present in skin biopsy specimens of patients with MF and its precursor form parapsoriasis en plaque but not in healthy tissue. In addition, the serum levels of CCL18 were increased threefold in MF patients compared with those in healthy controls. In skin, CCL18 was specifically expressed by CD163 ؉ CD209 ؉ macrophages at the invasive margin of the tumor and not expressed by mature CD208 ؉ dendritic cells in the center of the tumor. The chemokine CCL17 was, by contrast, ubiquitously expressed. Furthermore, CCL18 promoted the chemotaxis but not the proliferation of CTCL cells. CCL18 inhibited proliferation of tumor cells and abolished the CXCL12-induced growth of a CTCL cell line. These data link the increased expression of CCL18 with CTCL and suggest an immunomodulatory effect of the chemokine in the pathogenesis

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Section: Functional Impact Of Ccl18 On Ctcl Cell Linesmentioning

confidence: 99%

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

Günther

Zimmermann

Berndt

et al. 2011

The American Journal of Pathology

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“…In these last years, a number of studies have characterized the circulating neoplastic T lymphocytes of SS as CD45RO+, CCR4+CD26-CD27+CCR7+ cells (3)(4)(5)(6)(7). This immunophenotype resembles that observed for central memory T (T CM ) lymphocytes (8), and thus, as already proposed (6,9), SS cells might represent a neoplastic expansion of this T lymphocytes subset.…”

Section: Introductionmentioning

confidence: 98%

CXCL13 Is Highly Produced by Sézary Cells and Enhances Their Migratory Ability via a Synergistic Mechanism Involving CCL19 and CCL21 Chemokines

et al. 2008

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Chemokine and chemokine receptors expressed by normal and neoplastic lymphocytes play a key role in cell recruitment into skin and lymph nodes. The aim of this study was to get further insights into the role of chemokines in pathogenesis and progression of cutaneous T-cell lymphoma (CTCL) with particular regard to Sézary Syndrome (SS), a CTCL variant with blood involvement. Here, we show that functional CXCL13 homeostatic chemokine is strongly up-regulated in SS cells, well-detectable in skin lesions and lymph nodes, and measurable at high concentration in plasma of SS patients, at different levels during disease progression. Furthermore, we show that the addition of CXCL13 to CCL19 or to CCL21, the selective CCR7 agonists responsible for lymph node homing, strongly enhances the migration of CCR7+ SS cells. We also show that neutralization of the CCR7 receptor strongly impairs CCL19/21-induced chemotaxis of SS cells both in the absence or presence of CXCL13. Additional experiments performed to investigate the survival, adhesion, and metalloproteases secretion indicate that CXCL13 combined with CCL19 and CCL21 mainly affects the chemotaxis of SS cells. Our findings suggest that this newly described CXCL13 expression in SS represents a new pathogenetic mechanism of diagnostic significance. [Cancer Res 2008;68(17):7137-46]

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“…All the patients were enrolled in clinical protocols approved by the Ethical Committee of the Istituto Dermopatico dell'Immacolata, and informed consent was obtained in accordance with the Declaration of Helsinki. Diagnosis of SS was based on described criteria (16). The major clinical and immunologic characteristics, including T-cell receptor clonal analysis (17) of the samples, are listed in Supplementary Table S1.…”

Section: Methodsmentioning

confidence: 99%

Identification of Key Regions and Genes Important in the Pathogenesis of Sézary Syndrome by Combining Genomic and Expression Microarrays

et al. 2009

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In this study, we used single nucleotide polymorphism and comparative genomic hybridization array to study DNA copy number changes and loss of heterozygosity for 28 patients affected by Sézary syndrome (SS), a rare form of cutaneous Tcell lymphoma (CTCL). Our data identified, further confirming previous studies, recurrent losses of 17p13.2-p11.2 and 10p12.1-q26.3 occurring in 71% and 68% of cases, respectively; common gains were detected for 17p11.2-q25.3 (64%) and chromosome 8/8q (50%). Moreover, we identified novel genomic lesions recurring in >30% of tumors: loss of 9q13-q21.33 and gain of 10p15.3-10p12.2. Individual chromosomal aberrations did not show a significant correlation with prognosis; however, when more than three recurrent chromosomal alterations (gain or loss) were considered, a statistical association was observed using Kaplan-Meier survival analysis. Integrating mapping and transcriptional data, we were able to identify a total of 113 deregulated transcripts in aberrant chromosomal regions that included cancer-related genes such as members of the NF-κB pathway (BAG4, BTRC, NKIRAS2, PSMD3, and TRAF2) that might explain its constitutive activation in CTCL. Matching this list of genes with those discriminating patients with different survival times, we identify several common candidates that might exert critical roles in SS, such as BUB3 and PIP5K1B. Altogether, our study confirms and maps more precisely the regions of gain and loss and, combined to transcriptional profiles, suggests a novel set of genes of potential interest in SS. [Cancer Res 2009;69(21):8438-46]

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Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV

Cited by 153 publications

References 62 publications

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

CXCL13 Is Highly Produced by Sézary Cells and Enhances Their Migratory Ability via a Synergistic Mechanism Involving CCL19 and CCL21 Chemokines

Identification of Key Regions and Genes Important in the Pathogenesis of Sézary Syndrome by Combining Genomic and Expression Microarrays

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