B cell- and monocyte-activating chemokine (BMAC), a novel non-ELR α-chemokine

Zou

Molecular Medicine Reports

et al. 2014

Abstract. Chemokines are important in the proliferation and metastasis of tumors. CXCL14 is a member of the CXCL chemokine family and exhibits various expression patterns in different types of tumor, even those tumors that occur in the same type of tissue. The expression of CXCL14 and its clinical significance in colorectal carcinoma are unclear. In the present study, the expression levels of CXCL14 in colorectal carcinoma and adjacent normal tissues were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Kaplan-Meier survival curves and the Cox regression model were applied to evaluate the clinical significance of the expression levels of CXCL14 in colorectal carcinoma compared with those in normal tissues. To investigate the effects at a cellular level, a replication-defective lentivirus overexpressing CXCL14 was constructed and transfected into HT29 colorectal carcinoma cells. The effect of CXCL14 on the proliferation of colorectal carcinoma cells and the change in cell cycle distributions were investigated using a cell counting kit-8 assay and flow cytometry, respectively. Results of the current study indicated that the expression levels of CXCL14 mRNA and protein in colorectal carcinoma were markedly reduced compared with levels in normal tissues (P<0.05). The clinical correlation analysis suggested that downregulation of CXCL14 expression in tumors was associated with lymph metastasis, tumor location, and clinicopathological stage (P<0.05). Kaplan-Meier survival analysis revealed that downregulation of CXCL14 expression was correlated with a poor prognosis (P<0.01). Overexpression of CXCL14 by lentiviral transfection produced an inhibitory effect on cell proliferation by arresting the cell cycle in the G 1 stage. The data of the current study suggest that CXCL14 may be involved in the development and progression of colorectal carcinoma, and may act directly as a potential cancer suppressor gene. The level of CXCL14 expression may be a valuable adjuvant parameter in predicting the prognosis of colorectal carcinoma and may be a potential therapeutic target.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression and effect of CXCL14 in colorectal carcinoma

Zou

Molecular Medicine Reports

et al. 2014

“…CXCL14 was first identified by differential display of normal oral epithelial cells and head and neck squamous cell carcinoma when it was noted to be down-regulated in tumour specimens (60)(61)(62), but its mechanism of action, including its receptor, remain to be identified. CXCL14 was found to inhibit microvascular endothelial cell chemotaxis to CXCL8, bFGF, and VEGF in vitro and attenuate angiogenesis to these agonists in vivo (63).…”

Section: Chemokine-mediated Inhibition Of Angiogenesis Via Undefined mentioning

confidence: 99%

Chemokines as mediators of angiogenesis

Mehrad¹,

Keane²,

Strieter³

2007

Thromb Haemost

181

145

SummaryChemokines were originally described as cytokines that mediate leukocyte recruitment to sites of inflammation. Members of a subgroup of chemokines, the CXC family, also play a critical role in both physiologic and pathologic angiogenesis, including in the context of chronic inflammation, fibrosis, and malignancy. A unique feature of this family of cytokines is that, on the basis of their structure and receptor binding, individual ligands display either angiogenic or angiostatic biological activity in the regulation of angiogenesis. In this review, we summarize the key literature in this growing field.

“…The chemokine was first reported to be expressed in the breast and kidney but later was found in many other normal cells and tissues (10), whereas it was absent from or expressed in only a small amount in carcinoma cell lines in culture and cancerous tissues in vivo including OC cells (5,7,9,17). It was reported that mouse BRAK/CXCL14 activates B cells and monocytes (20) and stimulates dendritic cell infiltration into normal and tumor tissues (18). BRAK/CXCL14 also stimulates the migration of activated NK cells (21) and inhibits angiogenesis (17).…”

Section: Acknowledgementsmentioning

confidence: 99%

BRAK/CXCL14 expression in oral carcinoma cells completely suppresses tumor cell xenografts in SCID mouse

et al. 2009

SCID mice are a model of human severe combined immunodeficiency disease and are deficient in B cell function in addition to T cell function. Tumors from other species are easily transplanted into SCID mice and will grow without being rejected. We previously reported that the chemokine BRAK/CXCL14 is expressed in normal cells but its expression is down regulated in an in vitro cancer progression model, suggesting that it has the potential for antitumor activity. Here we report that the growth of BRAK/CXCL14 expression vector-transfected oral cancer cells was completely (100%) suppressed in SCID mouse xenografts even though mock-vector introduced control tumor cells grew well with 100% of animals developing tumors. In addition, suppression of xenografts was much faster and the rate was much higher in SCID mice than in T cell functiondeficient nude mice. These data indicate the possibility that BRAK expression inhibits tumor cell establishment by regulating interactions between tumor stem cells and NK cells and/or suppressing formation of tumor microvessels.Tumors develop in multiple steps (6,19,25), and tumor progression is dependent on the balance of the expression between tumor progression-promoting and -suppressing genes being in favor of the former at each step (1, 2). In order to prevent tumor progression, many investigators have searched for molecules that are over-expressed during tumor progression as target molecules for therapeutic drugs and have tried to prevent tumor progression by inhibiting these tumor-promoting molecules. However, drugs for many of the target molecules were not successful for clinical applications owing to the serious side effects of these drugs, which is not surprising because these target molecules are also important for normal development and maintenance of tissues and for homeostasis of our body (16,22).On the other hand, activation of presumptive tumor suppressor(s) or inhibition of their down-regulation may be much more promising for the prevention of tumor progression without significant side effects, because these molecules are supposedly present abundantly in normal tissues. In the course of our study to find an endogenous tumor suppressor(s) for oral cancers (OC), we searched for molecules down-regulated in OC cells when the cells were treated with epidermal growth factor (EGF), whose receptor is frequently overactivated in OC. The expression of BRAK, which is also known as CXC chemokine ligand 14 (CXCL14), was down-regulated significantly by the treatment of OC cells with EGF as observed by cDNA microarray analysis followed by reverse-transcriptase polymerase chain reaction analysis. In order to investigate whether BRAK/CXCL14 have a tumor-suppressing effect in vivo, we prepared BRAK/CXCL14-expression vector-transfected tongue tumor-derived cells (HSC-3 BRAK) and cloned them. No difference in the growth rates of these cells was observed in vitro