VCC-1, a novel chemokine, promotes tumor growth

Weinstein, Edward J.; Head, Richard D.; Griggs, David W.; Sun, Dengming; Evans, Robert J.; Swearingen, Michelle L.; Westlin, Marisa M.; Mazzarella, Richard

doi:10.1016/j.bbrc.2006.08.194

Cited by 62 publications

(116 citation statements)

References 17 publications

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“…3, B and C). Of interest, a previous study also found preliminarily that the CXCL17 transcript is tightly coexpressed with the VEGF transcript during breast and colon tumor formation, where CXCL17 is proposed to accelerate tumor angiogenesis (30). Therefore, our result in Fig.…”

Section: Discussionsupporting

confidence: 60%

“…Microarray analyses have indicated that the CXCL17 transcript is elevated dramatically in breast and colon tumors, where its level is tightly coregulated in concert with vascular endothelial growth factor (VEGF) expression. Because of the central role of VEGF in the growth and differentiation of vasculature, CXCL17 has also been suggested as a critical player in tumor angiogenesis (30). Interestingly, contrary to the previous results, CXCL17 is found to act as an antitumor factor during the pancreatic carcinogenesis.…”

mentioning

confidence: 63%

“…Although its physiological functions have not been clearly explored, two studies have proposed that CXCL17 might act as a chemokine that accelerates tumor progression (13,30). Overexpression of CXCL17 in NIH3T3 or hepatocellular carcinoma cells significantly promotes their tumor formation capability in nude mice.…”

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confidence: 99%

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CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor

Lee¹,

Wang²,

Lin³

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

106

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Lee WY, Wang CJ, Lin TY, Hsiao CL, Luo CW. CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor. Am J Physiol Endocrinol Metab 304: E32-E40, 2013. First published October 31, 2012; doi:10.1152/ajpendo.00083.2012.-Chemokines play pivotal roles in the recruitment of various immune cells to diverse tissues in both physiological and pathological conditions. CXCL17 is an orphan chemokine preliminarily found to be involved in tumor angiogenesis. However, its protein nature, as well as its endogenous bioactivity, has not been well clarified. Using real-time PCR, immunohistochemical staining, and Western blotting, we found that CXCL17 is highly expressed in both a constitutive and inducible manner in the rat gastric mucosa, where it undergoes endoproteolysis during protein maturation. The mature CXCL17 exhibited strong chemoattractant abilities targeting monocytes and macrophages, potentially through ERK1/2 and p38 but not JNK signaling. CXCL17 also induced the production of proangiogenic factors such as vascular endothelial growth factor A from treated monocytes. Furthermore, in contrast to other CXC chemokines that accelerate inflammatory responses, CXCL17 showed novel anti-inflammatory effects on LPS-activated macrophages. Therefore, our data suggest that CXCL17 in the gastric lamina propria may play an important role in tissue repair and anti-inflammation, both of which help to maintain the integrity of the gastric mucosa. endoproteolysis; macrophages; stomach CHEMOKINES ARE A GROUP OF CHEMOTACTIC CYTOKINES that govern the recruitment of various leukocytes to inflammation sites. In addition to promoting the trafficking of leukocytes, recent studies indicate that chemokines also play important roles in many aspects, including tumor growth, angiogenesis, organ sclerosis, and autoimmunity (21). Based on sequence homology and the numbers of amino acids between the first two cysteines, chemokines can be subdivided into C, CC, CXC, and CX 3 C subgroups (15). Chemokines bind to G protein-coupled receptors (GPCRs) on different target cells to initiate intracellular signaling cascades. Although the physiological roles and cognate receptors of most chemokines have been well characterized (34), the endogenous function as well as the receptor nature of CXCL17, the most recent chemokine ligand to be reported (17), are still unclear.CXCL17 was originally identified in 2006 by threading methods as having a protein structure similar to the CXC chemokine family (17). Although its physiological functions have not been clearly explored, two studies have proposed that CXCL17 might act as a chemokine that accelerates tumor progression (13,30). Overexpression of CXCL17 in NIH3T3 or hepatocellular carcinoma cells significantly promotes their tumor formation capability in nude mice. Microarray analyses have indicated that the CXCL17 transcript is elevated dramatically in breast and colon tumors, where its level is tightly coregulated in concert with vascular endothelial growth factor (VEGF) expression. Becau...

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Section: Discussionsupporting

confidence: 60%

mentioning

confidence: 63%

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CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor

Lee¹,

Wang²,

Lin³

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

106

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“…CXCL17 is expressed in mucosal tissues such as trachea, stomach, and colon (1,3). CXCL17 was reported to be highly expressed in epithelial cells and vascular endothelial cells (1).…”

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confidence: 99%

“…A newly discovered 119-aa CXC chemokine, CXCL17, was discovered by fine structure-based protein analysis and cDNA microarray analysis (1,2). CXCL17 is expressed in mucosal tissues such as trachea, stomach, and colon (1,3).…”

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confidence: 99%

CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells

Oka

Sugaya

Takahashi

et al. 2017

The Journal of Immunology

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CXCL17 is expressed in a variety of cancers and promotes tumor progression by recruiting myeloid-derived suppressor cells (MDSCs). MDSCs suppress tumor immunity by attracting regulatory T cells (Tregs) into tumor sites through CCL5. In this study, we examined the role of CXCL17 in skin disorders. CXCL17 mRNA levels in psoriasis skin, but not in lesional skin of atopic dermatitis or cutaneous T cell lymphoma, were significantly higher than those in normal skin. CXCL17 was mainly expressed in the epidermis, and IFN-γ dose-dependently increased CXCL17 expression by human keratinocytes in vitro. As CXCL17 mRNA expression was increased by treatment with imiquimod (IMQ), we examined the effects of CXCL17 in IMQ-induced psoriasis-like skin inflammation. Injection of recombinant CXCL17 into the ear before and during IMQ application decreased ear thickness, inflammatory cytokine expression, and the number of infiltrating cells compared with PBS injection. Flow cytometric analysis and immunofluorescent staining revealed that the numbers of MDSCs, which are CD11b+Gr-1+, and that of Tregs, which are CD4+CD25+, were higher in the ear of the CXCL17-injected mice than in PBS-injected mice. MDSCs, but not Tregs, showed chemotaxis to CXCL17 in vitro. When mice were injected with anti-CCL5 Ab or anti-CCL4 Ab simultaneously with recombinant CXCL17, ear thickness and cytokine expression increased to a similar level of mice treated with PBS and control IgG, suggesting that these chemokines were important for anti-inflammatory effects. Taken together, CXCL17 attenuates IMQ-induced psoriasis-like skin inflammation by recruiting MDSCs and Tregs, which may be important for regulating excessive inflammation in psoriasis skin.

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A comprehensive review of chemokine CXC17 (VCC1) in cancer, infection, and inflammation

Shabgah

Jadidi‐Niaragh

Ebrahimzadeh

et al. 2022

Cell Biology International

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A crucial component of the immune system are chemokiness. Chemokine's dysregulation has been linked to a number of pathological diseases. Recently, CXCL17, a chemokine belonging to the CXC subfamily, was identified. With regard to a number of physiological conditions and disorders, CXCL17 either has homeostatic or pathogenic effects. Some research suggests that CXCL17 is an orphan ligand, despite the fact that G protein-coupled receptor (GPR) 35 has been suggested as a possible receptor for CXCL17. Since CXCL17 is primarily secreted by mucosal epithelia, such as those in the digestive and respiratory tracts, under physiological circumstances, this chemokine is referred to as a mucosal chemokine.Macrophages and monocytes are the cells that express GPR35 and hence react to CXCL17. In homeostatic conditions, this chemokine has anti-inflammatory, antibacterial, and chemotactic properties. CXCL17 promotes angiogenesis, metastasis, and cell proliferation in pathologic circumstances like malignancies. However, other studies suggest that CXCL17 may have anti-tumor properties. Additionally, studies have shown that CXCL17 may have a role in conditions such as idiopathic pulmonary fibrosis, multiple sclerosis, asthma, and systemic sclerosis. Additionally,

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VCC-1, a novel chemokine, promotes tumor growth

Cited by 62 publications

References 17 publications

CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor

CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor

CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells

A comprehensive review of chemokine CXC17 (VCC1) in cancer, infection, and inflammation

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