Roles of SLC/CCL21 and CCR7 in Human Kidney for Mesangial Proliferation, Migration, Apoptosis, and Tissue Homeostasis

Banas, Bernhard; Wörnle, Markus; Berger, Thorsten; Nelson, Peter J.; Cohen, Clemens D.; Kretzler, Matthias; Pfirstinger, Jochen; Mack, Matthias; Lipp, Martin; Gröne, Hermann Josef; Schlöndorff, Detlef

doi:10.4049/jimmunol.168.9.4301

Cited by 84 publications

(74 citation statements)

References 50 publications

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“…The effect of CCL21, which is highly expressed in the lymph nodes, in cell proliferation, has previously been reported in haematopoietic (Ploix et al 2001) and mesangial cells (Banas et al 2002), but it has never been described in tumour cells. We examined the effect of CCR7 activation and demonstrated that cell proliferation is significantly increased after 48-and 72-h stimulation with CCL21.…”

Section: Discussionmentioning

confidence: 99%

Expression and function of the chemokine receptor CCR7 in thyroid carcinomas

Sancho

Vieira

Casalou

et al. 2006

Journal of Endocrinology

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The chemokine receptor CCR7 plays a critical role in lymphocyte and dendritic cell trafficking into and within lymph nodes, the preferential metastatic site for papillary (PTC) and medullary (MTC) thyroid carcinomas. In order to determine a possible role for CCR7 in mediating the metastatic behaviour of thyroid carcinomas, we analysed its expression in normal and tumoral thyroid tissues of different histotypes and studied the in vitro effects of its activation by the CCR7 ligand, CCL21. Using real-time quantitative-PCR, we observed that CCR7 expression was higher in PTCs and MTCs than in follicular and poorly differentiated thyroid carcinomas. CCR7 expression was ninefold higher in classic compared with follicular variants of PTCs, and its expression in MTCs was significantly correlated with lymph node metastases. Immunohistochemical staining for CCR7 showed protein expression in neoplastic thyroid cells, with higher intensity in PTCs, MTCs and their lymph node metastases (LNMs). We further showed that CCL21 stimulation of a CCR7-expressing thyroid tumour cell line (TPC-1) promotes cell proliferation and migration, and the chemotactic effect of CCL21 in these cells involves actin polymerization, increased b1-integrin expression and increased matrix metalloproteinase secretion. Taken together, our results demonstrate that CCR7 activation on thyroid carcinoma cells by CCL21 -a chemokine abundantly expressed in lymph nodes -favours tissue invasion and cell proliferation, and therefore may promote thyroid carcinoma growth and LNM.

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Section: Discussionmentioning

confidence: 99%

Expression and function of the chemokine receptor CCR7 in thyroid carcinomas

Sancho

Vieira

Casalou

et al. 2006

Journal of Endocrinology

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“…It has been reported that CCL21, CCL25, and CXCL12 are involved in protection from apoptosis. [43][44][45] Therefore, the decrease of CCL21, CCL25, and CXCL12 in SIV-infected lungs could contribute to increased apoptosis of host cells, which in turn could lead to increased stimulation of TLR3 by RNAladen apoptotic bodies. 46 IL-10 is an anti-inflammatory cytokine and can suppress Th1 lymphocyte responses and activation of macrophages.…”

Section: Discussionmentioning

confidence: 99%

Simian Immunodeficiency Virus Infection Alters Chemokine Networks in Lung Tissues of Cynomolgus Macaques

Qin

Junecko

Trichel

et al. 2010

The American Journal of Pathology

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Infection by HIV-1 frequently leads to pulmonary complications, including alterations to local immune environments. To better understand these alterations, we have examined in detail the patterns and levels of expression of chemokine, cytokine, and chemokine receptor mRNAs in lung tissues from 16 uninfected or simian immunodeficiency virus ( Pulmonary diseases are frequent complications of HIV-1 infection, affecting 75% to 85% of patients with AIDS.1 In addition, Pneumocystis carinii (now called Pneumocystis jirovecii in humans) pneumonia (PCP) is one of most frequent pulmonary opportunistic infections in HIV-1 infected individuals. However, little is known about the mechanisms leading to changes in pulmonary immune function and how these changes ultimately contribute to pathogenesis. Identifying alterations of overall immune function and the local mediators of these changes in the lungs during HIV-1 infection and AIDS will be useful for understanding and treating HIV-1-associated pulmonary complications.Chemokines are soluble immune factors that recruit cells bearing appropriate receptors into local environments as part of homeostatic immune cell trafficking and inflammatory reactions. There are approximately 50 known chemokines and 18 chemokine receptors.2 Chemokines play an important role in the control of infectious agents by recruiting effector cells to local inflammatory sites of infection and by serving directly as antimicrobial peptides.

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“…CCR7 expression did not consistently alter any of the in vitro growth features examined, including proliferation in the presence of CCL21. A few non-leukocyte cell types expressing chemokine receptors were reported to have increased proliferation in the presence of the appropriate chemokine; CCR7-positive kidney mesangial cells showed a proliferative response to CCL21 (25,26), whereas CXCR4-positive human pancreatic tumor cells had enhanced proliferation in the presence of CXCL12 (27). Our data show that CCR7-expressing mammary cancer cells behave differently from other CCR7-expressing non-leukocyte cell types.…”

Section: Discussionmentioning

confidence: 40%

Expression of a functional CCR7 chemokine receptor inhibits the post-intravasation steps of metastasis in malignant murine mammary cancer cells

et al. 2007

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Abstract.To study the role of the chemokine receptor CCR7 in the metastatic process, a murine CCR7 gene was transduced in two mammary cancer cell lines with different origins and molecular features; TS/A, derived from a spontaneous mammary cancer of BALB/c strain, and N202.1A, derived from a HER-2/neu transgenic mammary cancer (FVB background) and characterized by a high expression of HER-2/ neu. Transduced CCR7 conferred to mammary cancer cells a chemotactic response towards CCL21 (a CCR7 ligand), but did not consistently affect in vitro growth properties. In vivo, CCR7-engineered cells gave rise to tumors in syngeneic hosts with growth rates similar to or slightly lower than the controls and with similar patterns of spontaneous metastases. When injected directly intravenously to study the late post-intravasation phases of metastasis, CCR7-engineered cells showed a strongly decreased lung colonizing ability. Such an effect was observed both with HER-2/neu-positive and -negative mammary cancer cells. When used as a prophylactic vaccine, CCR7-transduced cell vaccine succeeded in the long-term control of mammary tumorigenesis in 25% of the HER-2/neu transgenic females, suggesting an increased immunogenicity of CCR7-engineered cells.

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Roles of SLC/CCL21 and CCR7 in Human Kidney for Mesangial Proliferation, Migration, Apoptosis, and Tissue Homeostasis

Cited by 84 publications

References 50 publications

Expression and function of the chemokine receptor CCR7 in thyroid carcinomas

Expression and function of the chemokine receptor CCR7 in thyroid carcinomas

Simian Immunodeficiency Virus Infection Alters Chemokine Networks in Lung Tissues of Cynomolgus Macaques

Expression of a functional CCR7 chemokine receptor inhibits the post-intravasation steps of metastasis in malignant murine mammary cancer cells

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