The chemokine CXCL14 (BRAK) stimulates activated NK cell migration: Implications for the downregulation of CXCL14 in malignancy

Starnes, Trevor; Rasila, Kanwaldeep Kaur; Robertson, Michael J.; Brahmi, Zacharie; Dahl, Richard; Christopherson, Kent W.; Hromas, Robert

doi:10.1016/j.exphem.2006.05.015

Cited by 124 publications

(88 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These data also indicate that BRAK expression is essential for tumor suppression in vivo (14). The same or a higher level of natural killer (NK) cell activity is present in SCID mice compared with wild-type C.B-17 mice (26); and BRAK/CXCL14 stimulates the migration of activated NK cells but does not affect the proliferation or cytotoxic activity of normal NK cells (21), suggesting that NK cells are partially responsible for BRAK/CXCL14-dependent tumor suppression and that the co-presence of a NK cell activator(s) is essential for tumor suppression. It is also reported that tumor angiogenesis is important for tumor growth and progression (4,12,23) and that BRAK/CXCL14 was shown to have angiostatic (anti-angiogenic) activity (17).…”

mentioning

confidence: 73%

“…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). Accumulating evidence indicates that cancers grow from cancer stem cells (24) and that tumors progress by interacting with the tumor microenvironment, which is composed of stroma, inflammatory cells and recruited vasculature (3).…”

Section: Acknowledgementsmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2009

View full text Add to dashboard Cite

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

show abstract

mentioning

confidence: 73%

Section: Acknowledgementsmentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

show abstract

“…CXCL14 showed the greatest change in expression of any gene (>4-fold), greater even than RhoBTB2 (Figure 1). CXCL14 is expressed by epithelial cells (Hromas et al, 1999;Frederick et al, 2000) and is a chemokine for monocytes (Kurth et al, 2001), natural killer cells (Starnes et al, 2006) and immature dendritic cells (Shellenberger et al, 2004;Schaerli et al, 2005). CXCL14 expression is lost at high frequency in wide range of epithelial tumors (Hromas et al, 1999;Frederick et al, 2000;Schwarze et al, 2002;Shellenberger et al, 2004;Shurin et al, 2005), although the mechanism for this loss is unknown.…”

Section: Resultsmentioning

confidence: 99%

The atypical Rho GTPase RhoBTB2 is required for expression of the chemokine CXCL14 in normal and cancerous epithelial cells

et al. 2008

View full text Add to dashboard Cite

The Rho family of small GTPases control cell migration, cell invasion and cell cycle. Many of these processes are perturbed in cancer and several family members show altered expression in a number of tumor types. RhoBTB2/ DBC2 is an atypical member of this family of signaling proteins, containing two BTB domains in addition to its conserved Rho GTPase domain. RhoBTB2 is mutated, deleted or silenced in a large percentage of breast and lung cancers; however, the functional consequences of this loss are unclear. Here we use RNA interference in primary human epithelial cells to mimic the loss of RhoBTB2 seen in cancer cells. Through microarray analysis of global gene expression, we show that loss of RhoBTB2 results in downregulation of CXCL14-a chemokine that controls leukocyte migration and angiogenesis, and whose expression is lost through unknown mechanisms in a wide range of epithelial cancers. Loss of RhoBTB2 expression correlates with loss of CXCL14 secretion by head and neck squamous cell carcinoma cell lines, whereas reintroduction of RhoBTB2 restores CXCL14 secretion. Our studies identify CXCL14 as a gene target of RhoBTB2 and support downregulation of CXCL14 as a functional outcome of RhoBTB2 loss in cancer.

show abstract

“…33,45 Uterine expression of CXCL14 may also play a role in uterine NK-cell recruitment during the early pregnancy. 46 However, a clear picture of the effects of CXCL14 on uterine NK-cell recruitment in the context of the uterus is still vague, since a report using knockout models indicates opposite effects of its chemoattractant roles on many types of leukocytes. 47 These studies suggest that NK cells use more than one type of receptor-ligand pairing to enter the uterus, and these chemokines may act sequentially or in combination to contribute to the accumulation of NK cells in the decidual tissues.…”

Section: Recruitment Of Nk Cellsmentioning

confidence: 99%

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

2014

View full text Add to dashboard Cite

Embryos express paternal antigens that are foreign to the mother, but the mother provides a special immune milieu at the fetal-maternal interface to permit rather than reject the embryo growth in the uterus until parturition by establishing precise crosstalk between the mother and the fetus. There are unanswered questions in the maintenance of pregnancy, including the poorly understood phenomenon of maternal tolerance to the allogeneic conceptus, and the remarkable biological roles of placental trophoblasts that invade the uterine wall. Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. It is increasingly evident that the gestational uterine microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the maternal-fetal interface and regulate multiple events that are closely associated with normal pregnancy. Here, we review the expression and function of chemokines and their receptors at the maternal-fetal interface, with a special focus on chemokine as a key component in trophoblast invasiveness and placental angiogenesis, recruitment and instruction of immune cells so as to form a fetus-supporting milieu during pregnancy. The chemokine network is also involved in pregnancy complications.

show abstract

The chemokine CXCL14 (BRAK) stimulates activated NK cell migration: Implications for the downregulation of CXCL14 in malignancy

Cited by 124 publications

References 21 publications

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

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

The atypical Rho GTPase RhoBTB2 is required for expression of the chemokine CXCL14 in normal and cancerous epithelial cells

The integrative roles of chemokines at the maternal–fetal interface in early pregnancy

Contact Info

Product

Resources

About