Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer

Ghadjar, Pirus; Loddenkemper, Christoph; Coupland, Sarah E.; Stroux, Andrea; Noutsias, Michel; Thiel, Eckhard; Christoph, Frank; Miller, Kurt; Scheibenbogen, Carmen; Keilholz, Ulrich

doi:10.1007/s00432-008-0403-5

Cited by 43 publications

(35 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, motility and invasiveness abilities of HCCLM6 cells were maintained in untreated HCCLM6 cells. The underlying mechanisms are attributed to the blockade of the activation of CCR6 pathway, which further inhibit the expression of invasion and metastasis-related genes and proteins [24]. The results confirmed that both nucleolin and CCR6 act as an appropriate target to inhibit the migration and invasion of HCC.…”

Section: Discussionsupporting

confidence: 72%

The involvement of cell surface nucleolin in the initiation of CCR6 signaling in human hepatocellular carcinoma

et al. 2015

View full text Add to dashboard Cite

In recent years, the chemokine CC receptor 6 (CCR6) and its ligand CCL20 were reported to play an essential role in hepatocellular carcinoma (HCC). However, the role of cell surface nucleolin in the CCR6 pathway of HCC is not well featured. Using immunohistochemistry, Western blotting, siRNA, wound healing and transwell assay, we investigated the relationships of cell surface nucleolin and CCR6 signaling in HCC. In the present study, our findings identified that cell surface nucleolin and CCR6 protein were stained in most of HCC tissues (64, 68 %, respectively) and differently expressed in HCC cell lines; meanwhile, both expression has an association with advanced stage, lymph node metastasis and poor 5-year prognosis. According to in vitro assays, we found that the silencing of either cell surface nucleolin or CCR6 inhibited the protein expression of p-ERK, p-AKT, MMP2, MMP9 and ICAM-1 in the CCL20-stimulated HCCLM6 cells. Functional analysis revealed that cell surface nucleolin or CCR6 silencing significantly hampered HCCLM6 cell motility and invasiveness ability, when compared with control. In conclusion, this work suggests that cell surface nucleolin participates in the initiation of CCR6 pathway and biological behaviors of HCC, leading to HCC cell adhesion, migration and invasive behavior. In the clinical practice, cell surface nucleolin and CCR6 are recommended to predict poor prognosis and be used as a useful target for HCC patients.

show abstract

Section: Discussionsupporting

confidence: 72%

The involvement of cell surface nucleolin in the initiation of CCR6 signaling in human hepatocellular carcinoma

et al. 2015

View full text Add to dashboard Cite

show abstract

“…52 The profound increase in CCL20 expression (ϳ25ϫ) and its receptor CCR6 (ϳ5ϫ) is of particular significance as increased CCR6 expression has been associated with advanced and aggressive PCa and CCL20/CCR6 have also been suggested as novel treatment target molecules for PCa. 31 The increased expression of CCL8, CCR5, and CCR2 in the AROMϩ tissues is also particularly significant (increased ϳ10ϫ, ϳ3ϫ, and ϳ4ϫ, respectively). Although the role of CCL8 in the prostate is unknown, this chemokine elicits its effects by binding to the receptors CCR5 and CCR2.…”

Section: Estrogens Prostatitismentioning

confidence: 97%

“…Of particular significance were significant increases in the expression of CCL20, CCL8, CCR6, CCR5, and CCR2, all of which have been implicated in the development of PCa. 31,32,33 …”

Section: Chronic Inflammation As a Cause Of Prostatic Premalignancymentioning

confidence: 99%

Increased Endogenous Estrogen Synthesis Leads to the Sequential Induction of Prostatic Inflammation (Prostatitis) and Prostatic Pre-Malignancy

Ellem

Wang

Poutanen

et al. 2009

The American Journal of Pathology

View full text Add to dashboard Cite

Prostatitis causes substantial morbidity to men, through associated urinary symptoms, sexual dysfunction, and pelvic pain; however, 90% to 95% of cases have an unknown etiology. Inflammation is associated with the development of carcinoma, and, therefore, it is imperative to identify and study the causes of prostatitis to improve our understanding of this disease and its role in prostate cancer. As estrogens cause prostatic inflammation, here we characterize the murine prostatic phenotype induced by elevated endogenous estrogens due to aromatase overexpression (AROM؉). Early-life development of the AROM؉ prostate was normal; however, progressive changes culminated in chronic inflammation and pre-malignancy. The AROM؉ prostate was smaller at puberty compared with wild-type controls. Mast cell numbers were significantly increased at puberty and preceded chronic inflammation, which emerged by 40 weeks of age and was characterized by increased mast cell, macrophage, neutrophil, and T-lymphocyte numbers. The expression of key inflammatory mediators was also significantly altered, and premalignant prostatic intraepithelial neoplasia lesions emerged by 52 weeks of age. Taken together, these data link estrogens to prostatitis and premalignancy in the prostate, further implicating a role for estrogen in prostate cancer. These data also establish the AROM؉ mouse as a novel, non-bacterial model for the study of prostatitis. Prostatitis, an exceedingly common condition in the male population worldwide, has an incidence of ϳ9% and a prevalence of ϳ14%, and, unlike benign prostatic hyperplasia and prostate cancer (PCa), which are predominantly diseases of older men, prostatitis afflicts men of all ages. It is also the most common outpatient condition seen in men under 50 years of age and accounts for more clinical visits than either PCa and/or benign prostatic hyperplasia.1,2 At present our knowledge of prostatitis is lacking, with 90% to 95% of cases having an unknown etiology. This represents a significant problem, particularly as prostatitis has also been implicated in the development of PCa.3-5 Given the prevalence of prostatitis and this putative link to PCa, it is vitally important to identify the unknown causes of prostatitis.Several causes of prostatitis have been postulated, including hormonal variation or exposure, infection due to sexually transmitted disease, 6 dietary factors, and physical trauma from urine reflux. 7 However, of particular interest is an apparent link between estrogen and prostatic inflammation, 8 which has emerged mainly from the administration of pharmacological levels of exogenous estrogen to rodents.9 Additional data obtained from further rodent studies show that the prostate gland is particularly sensitive to estrogenic exposure during development in fetal and neonatal life; transient estrogen exposure before puberty results in inflammation later in life, well after the exposure has occurred.10,11 Several decades of research from various laboratories, including our own, has demonstrated that...

show abstract

“…Members of the CCR family are also used by tumor cells to spread to specific tissues such as the skin, the gut and the liver. CCR6 plays a role in organ selective liver metastasis of colorectal cancer [107,108]. The skin-homing receptors CCR4 and CCR10 were found expressed together with CCR3 in cutaneous lymphoma [109][110][111].…”

Section: Tumor Cell Invasion and Migration To Distant Organsmentioning

confidence: 99%

Chemokines in cancer related inflammation

Allavena

Germano

Marchesi

et al. 2011

Experimental Cell Research

201

140

View full text Add to dashboard Cite

Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis.Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies

show abstract

Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer

Cited by 43 publications

References 25 publications

The involvement of cell surface nucleolin in the initiation of CCR6 signaling in human hepatocellular carcinoma

The involvement of cell surface nucleolin in the initiation of CCR6 signaling in human hepatocellular carcinoma

Increased Endogenous Estrogen Synthesis Leads to the Sequential Induction of Prostatic Inflammation (Prostatitis) and Prostatic Pre-Malignancy

Chemokines in cancer related inflammation

Contact Info

Product

Resources

About