Chemokine Receptor CCR7 Expression Correlates with Lymph Node Metastasis in Pancreatic Cancer

Nakata, Bunzo; Fukunaga, Shinya; Noda, Eiji; Amano, Ryosuke; Yamada, Noriko; Hirakawa, Kosei

doi:10.1159/000139126

Cited by 53 publications

(44 citation statements)

References 42 publications

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“…CCL5 is a predictor of worse disease progression of stage II breast cancer patients [45,53]. CCL19, CCL21 played a prominent role in lymph node metastasis in many solid tumors [1,2,[54][55][56]. Multiple CXC chemokines were coexpressed in CXCL8-positive breast tumors and accounted for the higher aggressiveness of these types of tumors [57].…”

Section: Discussionmentioning

confidence: 99%

Coexpression of atypical chemokine binders (ACBs) in breast cancer predicts better outcomes

Xiao

et al. 2010

Breast Cancer Res Treat

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Some evidence suggests that atypical chemokine binders (ACBs) including DARC, D6, and CCX-CKR play an important role in inhibiting invasion and metastasis of cancer cells; however, their expression in breast cancer has not been well characterized. The purpose of this study was to determine the predictive value of ACBs for relapse-free survival and overall survival in breast cancer. The expressions of the three molecules were analyzed immunohistochemically in a total of 558 consecutive breast specimens comprising 12 normal breast tissues, 29 noninvasive (carcinoma in situ), and 517 invasive breast carcinoma and their relationships to clinicopathological features and survival were investigated in invasive breast cancer. Coexpression of ACBs in invasive breast carcinoma (55.9%) was much lower that of noninvasive breast carcinoma (93.1%) and normal breast tissue (100.0%), P = 0.0004, 0.0096, respectively. Their separate stainings in invasive cancer were significantly conversely correlated with lymph node status and tumor stage. In univariate analysis, the three proteins and their coexpression were significantly associated with higher relapse-free survival and overall survival. In multivariate analysis, each of these molecules was favorable for relapse-free survival, but not overall survival. Surprisingly, their coexpression was not only independently prognostic factor for relapse-free survival (RR = 0.182, 95% CI: 0.101-0.327, P < 0.001), but also for overall survival (RR = 0.271, 95% CI: 0.081-0.910, P = 0.035). These findings highlight that the multiple loss of ACBs may occur during the development of tumorigenesis and their coexpression in breast cancer is predictive of favorable outcomes.

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Section: Discussionmentioning

confidence: 99%

Coexpression of atypical chemokine binders (ACBs) in breast cancer predicts better outcomes

Xiao

et al. 2010

Breast Cancer Res Treat

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“…Nearly all these chemoattractant cytokines are soluble, small molecular weight (8)(9)(10)(11)(12)(13)(14) proteins. Based on the positioning and number of the conserved N-terminal cysteine residues of the chemokines, they are classified into four subfamilies: CXC, CC, CX3C and C chemokines.…”

Section: The Chemokine Superfamilymentioning

confidence: 99%

“…Since then, the *Address correspondence to this author at the Department of DermatologyFroedtert Clinics, Medical College of Wisconsin, 9200 W. Wisconsin Ave., Milwaukee, WI 53226, USA; Tel: 414-955-3100; Fax: 414-955-6221; E-mail: sthwang@mcw.edu chemokine-receptor pair of CXCR4 and CXCL12 has been implicated in 26 different types of cancer with multiple potential roles in cancer growth and metastasis [6][7][8][9]. Other pairs, such as CCR7, which is expressed in multiple cancers, and its ligand CCL21, which is highly expressed by lymphatic endothelial cells and by stromal cells in the lymph nodes, have been shown to be mediators of lymph node metastasis [10][11][12][13][14]. CXCR3, CCR1 and CX3CR1 have also been described to play potential roles in cancer biology [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Chemokine Receptors as Targets for Cancer Therapy

Lee

Chevalier

et al. 2009

CPD

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Chemokines and their receptors play critical roles in leukocyte trafficking during inflammatory processes. Although the role of chemokine receptors (CKRs) in cancer biology is a relatively new field of study, a growing body of data suggest that a number of CKRs, including CXCR4, CCR4, CCR7, and CCR10, may play diverse of roles in cancer growth, cancer metastasis, cancer angiogenesis, or the composition of the cancer microenvironment. Preclinical models of cancer indicate that cancer antagonists, most notably those for CXCR4, can block cancer growth either directly or by altering the cancer stroma. Highthroughput screening methods to identify effective CKR antagonists have been developed, but specificity, potency, and drug-delivery of validated candidate compounds remain issues that result in the clinical failure of many initially promising candidates. The recent approval of a CCR5 receptor antagonist in HIV suggests that safe, effective small molecular antagonists for other CKRs may not be far away. There is still a clear need to extend our understanding of the signalling pathways by which CKRs facilitate cancer processes. Because of the role of CKRs in cancer cell survival, the combination of CKR antagonists with traditional chemotoxic agents or with immunotherapy is an alluring strategy since this increases the specificity of treatment to the cancer and potentially limits additional systemic side effects.

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“…13,14 The expression of CCR7, a member of the G protein-coupled receptor family, on lymphocytes directs their homing to lymph node, coordinates primary immune responses, and induces peripheral immune tolerance. 15 CCR7 expression on tumor cells has been reported and shown to play a pivotal role in lymph node metastasis of various cancers such as breast, 16 pancreatic, 17 thyroid, 18 and colorectal 19 cancers; oral squamous cell carcinoma 20 ; melanoma 21 ; and lymphoma. 22 Lymph node involvement in these cancers is generally associated with poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Engineering lymph node homing of ex vivo–expanded human natural killer cells via trogocytosis of the chemokine receptor CCR7

Somanchi

Cooper

et al. 2012

Blood

108

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Until recently, the main limiting factor to the clinical application and efficacy of NK cells was the difficulty in obtaining sufficient cell numbers for adoptive transfer. Development of novel methods of expanding primary human NK cells ex vivo has renewed interest in NK cells for immunotherapy for cancer. [2][3][4][5][6] Expanded NK cells have enhanced expression of activating receptors, 4,7,8 that in turn improves their antitumor cytotoxicity. Where activating receptors did not sufficiently elicit an antitumor response, researchers augmented the antitumor effect of NK cells by expression of chimeric Ag receptors. 9-11 Ultimately, the success of NK cell adoptive immunotherapy for cancer depends not only on target recognition but also on homing of NK cells to the tumor target in vivo. Thus, the effector cells must express the appropriate chemokine receptors.Cancer cells express a wide array of chemokines and chemokine receptors that are instrumental in tumor survival 12 and metastatic spread. 13 Lymph nodes, particularly the tumor-draining nodes, are the foci of metastatic spread of tumors for a vast number of cancer types. 13,14 The expression of CCR7, a member of the G protein-coupled receptor family, on lymphocytes directs their homing to lymph node, coordinates primary immune responses, and induces peripheral immune tolerance. 15 CCR7 expression on tumor cells has been reported and shown to play a pivotal role in lymph node metastasis of various cancers such as breast, 16 pancreatic, 17 thyroid, 18 and colorectal 19 cancers; oral squamous cell carcinoma 20 ; melanoma 21 ; and lymphoma. 22 Lymph node involvement in these cancers is generally associated with poor prognosis.Peripheral NK cells express a variety of chemokine receptors such as CXCR1, CXCR3, and CXCR4 with subsets expressing CCR1, CCR4, CCR5, CCR6, CCR7, CCR9, CXCR5, and CXCR6. Expression of CCR7 on NK cells can facilitate homing to lymph nodes, which, in the context of adoptive immunotherapy for various cancers, would offer a main advantage in targeting lymph node metastases. However, CD56 bright CD16 Ϫ NK cells, which primarily secrete cytokines, express CCR7, but CD56 dim CD16 ϩ NK cells, which are primarily responsible for cytotoxicity, do not. 23 In a previous study, we reported that expanded NK cells are predominantly of CD56 ϩ CD16 bright phenotype and did not express CCR7. 7 In this study, we sought to express CCR7 on expanded NK cells ex vivo to facilitate lymph node homing on adoptive transfer. Although investigators have used viral vectors to gene modify NK cell lines 10,24 and primary NK cells, 9,25 because of safety concerns over integrating viral vectors there has been a recent shift in emphasis toward nonviral methods of gene transfer, particularly nonintegrating, mRNA-based electroporation approaches. 11 However, electroporation of NK cells has been difficult in that the transfection efficiency and viability of NK cells are low, and high-throughput electroporation methods for gene modifying clinically relevant NK cell numbers are ...

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Chemokine Receptor CCR7 Expression Correlates with Lymph Node Metastasis in Pancreatic Cancer

Cited by 53 publications

References 42 publications

Coexpression of atypical chemokine binders (ACBs) in breast cancer predicts better outcomes

Coexpression of atypical chemokine binders (ACBs) in breast cancer predicts better outcomes

Chemokine Receptors as Targets for Cancer Therapy

Engineering lymph node homing of ex vivo–expanded human natural killer cells via trogocytosis of the chemokine receptor CCR7

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