Expression of the chemokine receptor CCR7 in prostate cancer presenting with generalized lymphadenopathy: Report of a case, review of the literature, and analysis of chemokine receptor expression

Heresi, Gustavo A.; Wang, Jingcheng; Taichman, Russell S.; Chirinos, Julio A.; Regalado, Jacinto; Lichtstein, Daniel M.; Rosenblatt, Joseph D.

doi:10.1016/j.urolonc.2005.02.004

Cited by 34 publications

(25 citation statements)

References 33 publications

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“…Furthermore, aberrantly increased CCR7 expression has been reported in breast (18,25), gastric (22,26,27), colorectal (28–30), non-small cell lung (31,32), cervical (33), SCC of the head and neck (34), prostate (35,36), melanoma (37) and esophageal, oral and oropharyngeal SCC cancer (38–41) and is generally associated with lymph node metastasis and worse prognosis. In addition, a previous study conducted at our institution in which the CCR7 expression levels in 115 patients with UBC and 10 patients with benign prostatic hyperplasia (BPH) were compared found a significantly higher frequency of detectable CCR7 expression in the UBC group than in the BPH group and the clinical feasibility of CCR7 expression level as an independent predictive biomarker in the diagnosis of lymph node metastasis (42).…”

Section: Discussionmentioning

confidence: 99%

CCL21/CCR7 interaction promotes cellular migration and invasion via modulation of the MEK/ERK1/2 signaling pathway and correlates with lymphatic metastatic spread and poor prognosis in urinary bladder cancer

Xiong

Huang

et al. 2017

International Journal of Oncology

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Lymph node metastasis in patients with urinary bladder cancer (UBC) is always associated with poor prognosis and is the determinant for tumor staging and the development of treatment regimens; however, its underlying mechanisms remain to be studied. Immunohistochemical staining of tumor sections from 62 UBC patients was performed using CCR7, D2-40 and CD34 antibodies. We showed that increased CCR7 expression was significantly associated with positive lymph node status (P=0.008), pT3-T4 tumor stage (P=0.015), tumor grade (P=0.010) and worse overall survival (OS, P<0.001) and that both CCR7 expression and lymph node metastasis were independent prognostic factors for OS (P=0.031 and P=0.001, respectively) based on multivariate analysis. We found that there was a significant association between MLVD and lymph node status (P=0.006), but this relation was not observed for MVD. Furthermore, we showed that increased CCR7 expression correlated significantly with higher MLVD (P=0.014) and MVD (P=0.002). Wound-healing and Matrigel Transwell assays indicated that activation of CCR7 with CCL21 significantly enhanced the invasion and migration abilities of UM-UC-3 cells, and this enhanced effect was significantly abrogated by CCR7 knockdown using siRNA. Western blot analysis revealed that the phospho-ERK1/2 level was markedly increased when UM-UC-3 cells were treated with CCL21 and significantly decreased when the CCR7 gene was silenced. MEK/ERK1/2 inhibition with PD98059 significantly suppressed the migration and invasion abilities of UM-UC-3 cells and also significantly abrogated the effects of CCL21/CCR7 on cell migration and invasion. Based on these results, we conclude that activation of the CCL21/CCR7 chemoaxis promotes lymph node metastasis of UBC in at least two ways. Firstly, although CCR7 is a promoting factor that induces both lymphangiogenesis and angiogenesis, it may promote lymph node metastasis through its lymphangiogenic effect rather than through its angiogenic effect. Secondly, the CCL21/CCR7 chemoaxis promotes the migration and invasion of UBC cells via the MEK/ERK1/2 signaling pathway rather than the PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

CCL21/CCR7 interaction promotes cellular migration and invasion via modulation of the MEK/ERK1/2 signaling pathway and correlates with lymphatic metastatic spread and poor prognosis in urinary bladder cancer

Xiong

Huang

et al. 2017

International Journal of Oncology

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“…Indeed, it is widely held that the CXCL12-CXCR4 pathway plays a major role in PCa metastasis. 14–16 Recently, CXCR3 17 , CXCR7 18 , CX3CR1 19 , CCR5 20 , CCR7 21 , and CCR9 22 have been shown to be involved in the adhesion, migration, and/or invasion of PCa cells. It is therefore likely that multiple chemokine receptors are involved in directing the multi-step process of PCa progression, including MMP expression.…”

Section: Introductionmentioning

confidence: 99%

Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell lines

Singh

et al. 2009

Intl Journal of Cancer

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Chemokines and chemokine receptors, has been shown to be involved in metastatic process of prostate cancer (PCa). In this study, we have show that primary PCa tissues and cell lines (LNCaP and PC3) express CXCR5, a specific chemokine receptor for the CXCL13. Expression of CXCR5 was significantly higher (P < 0.001) in PCa cases than compared to normal match (NM) tissues. CXCR5 intensity correlated (R2 = 0.97) with Gleason score. While prostate tumor tissues with Gleason scores ≥ 7, displayed predominantly nuclear CXCR5 expression patterns, PCa specimens with Gleason scores ≤ 6 showed predominantly membrane and cytoplasmic expression patterns that were comparable to benign prostatic hyperplasia (BPH). Similar to tissue expression, PCa cell lines expressed significantly more CXCR5 than normal prostatic epithelial cells (PrECs) and CXCR5 expression was distributed among intracellular and extracellular compartments. Functional in vitro assays showed higher migratory and invasive potentials toward CXCL13, an effect that was CXCR5-mediated. In both PCa cell lines, CXCL13 treatment increased the expression of collagenase-1 or matrix metalloproteinase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), stromalysin-2 (MMP-10), and stromelysin-3 (MMP-11). These data demonstrate the clinical and biological relevance of the CXCL13-CXCR5 pathway and its role in PCa cell invasion and migration.

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“…The mechanisms of metastasis are complex and incompletely understood, but it is apparent from our case that a favourable histology alone does not preclude widespread and aggressive metastatic disease. In this regard, genetic13 and microenvironmental factors14 15 have been shown to be instrumental in the development of aggressive metastatic disease.…”

Section: Discussionmentioning

confidence: 99%

Superior vena cava syndrome as a presentation of metastatic prostate cancer

Yun

Ershler

2012

BMJ Case Reports

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SummarySuperior vena cava (SVC) syndrome is an uncommon complication of malignant disease caused by the obstruction of venous blood flow in the SVC. When present, a diagnosis of lung cancer or lymphoma will be made in approximately 95% of cases. Although other malignant diseases are occasionally associated with SVC, its occurrence in patients with prostate cancer is rare. We present a case of a patient presenting with SVC obstruction who was subsequently diagnosed with prostate adenocarcinoma. The patient has been successfully treated with GnRH agonist. This case reflects the importance of a full clinical assessment and pathological confirmation of suspected tumour prior to treatment. BACKGROUND

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Expression of the chemokine receptor CCR7 in prostate cancer presenting with generalized lymphadenopathy: Report of a case, review of the literature, and analysis of chemokine receptor expression

Cited by 34 publications

References 33 publications

CCL21/CCR7 interaction promotes cellular migration and invasion via modulation of the MEK/ERK1/2 signaling pathway and correlates with lymphatic metastatic spread and poor prognosis in urinary bladder cancer

CCL21/CCR7 interaction promotes cellular migration and invasion via modulation of the MEK/ERK1/2 signaling pathway and correlates with lymphatic metastatic spread and poor prognosis in urinary bladder cancer

Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell lines

Superior vena cava syndrome as a presentation of metastatic prostate cancer

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