CCL21 promotes the migration and adhesion of highly lymph node metastatic human non-small cell lung cancer Lu-99 in vitro

Koizumi, Keiichi; Kozawa, Yoko; Ohashi, Yasukata; Nakamura, Eliane Shizuka; Aozuka, Yasushi; Sakurai, Hiroaki; Ichiki, Katsuyuki; Doki, Yoshinori; Misaki, Takuro; Saiki, Ikuo

doi:10.3892/or.17.6.1511

Cited by 33 publications

(45 citation statements)

References 19 publications

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“…Chemokines and their corresponding receptors have established roles in directing cell migration in many different types of cancer; and expression levels of these proteins have also correlated with clinical outcomes [24][25][26][27][28][29]. The role of CCL25-CCR9 signaling in modulating metastasis was initially reported by Letsch There is an absence of CCL25 staining within the normal architecture of the pancreatic duct and stroma c. In the malignant pancreatic lesion, with characteristic nuclear crowding, enlarged nuclei, and rare mitoses, there is moderate heterogeneous immunostaining for CCL25 protein in the nuclei.…”

Section: Discussionmentioning

confidence: 99%

Paracrine Activation of Chemokine Receptor CCR9 Enhances The Invasiveness of Pancreatic Cancer Cells

Heinrich

Arrington

et al. 2013

Cancer Microenvironment

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Chemokine receptors mediate cancer progression and metastasis. We have previously examined chemokine receptor CCR9 expression in pancreatic cancer. Here, our objective was to evaluate pancreatic stellate cells (PSCs) as a source of CCL25, the CCR9 ligand, and as an activator of CCL25-CCR9 signaling in pancreatic cancer cells. CCL25 and CCR9 expression levels in human pancreatic cancer tissues and normal human pancreas were assessed by immunohistochemsitry. In vitro secretion of CCL25 in PSCs and PANC-1 cells was verified by enzyme-linked immunosorbent assay. Pancreatic cancer cell invasion was measured using a modified Boyden chamber assay with CCL25, PSC secreted proteins, and PANC-1 secreted proteins as the chemoattractant. There was immunostaining for CCR9 expression in human pancreatic tumor tissues, but not in normal pancreatic tissue. CCL25 expression was absent in the normal pancreatic tissue sample, but was observed in cancer cells and in the stromal cells surrounding the tumor. In vitro, both PANC-1 cells and PSCs secreted CCL25. In an invasion assay, exposure to CCL25, PSC-and PANC-1-conditioned media significantly increased the invasiveness of PANC-1 cells. Inclusion of a CCR9-neutralizing antibody in the invasion assay blocked the increase in invading cells elicited by the chemoattractants. Our studies show that pancreatic cancer invasiveness is enhanced by autocrine and paracrine stimulation of CCR9. PSCs in the tumor microenvironment appear to contribute to paracrine activation of CCR9. Investigations into CCR9 as a potential therapeutic target in pancreatic cancer must consider cancer cell autocrine signaling and also paracrine signaling from interactions in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Paracrine Activation of Chemokine Receptor CCR9 Enhances The Invasiveness of Pancreatic Cancer Cells

Heinrich

Arrington

et al. 2013

Cancer Microenvironment

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“…Signal transduction through these proteins leads to the activation of g proteins and phospholipase c and the elevation of cytosolic free calcium. The chemokine ccL21 induces the adhesion of non-small lung cancer cells to vascular cell adhesion molecule-1 (vcAM-1) by activating integrin through a g protein-coupled receptor (22).…”

Section: Discussionmentioning

confidence: 99%

“…Migration was assayed in Transwell filter insert chambers (8 µm pore size; corning costar) as previously described (4,11,22). The upper surface of the chamber contained a Transwell filter (8-µm pore size polyvinyl pyrrolidone-free).…”

Section: Methodsmentioning

confidence: 99%

“…CXCR4 chemokine receptor mediates prostate tumor cell adhesion through α5 and β3 integrins (21). ccL21 promotes the migration and adhesion of lymph node metastases of human non-small cell lung cancer via integrins (22). Binding of the chemokine ccL19/ccL21 to its receptor, ccR7, increases adhesive properties of human mesangial cells by regulating integrins (23).…”

Section: Introductionmentioning

confidence: 99%

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Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvβ3

Liu¹,

Sun²,

Zhao³

et al. 2011

Int J Mol Med

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Abstract. The mechanisms leading to squamous cell carcinoma of the head and neck (SccHN) metastasis are incompletely understood. Although evidence shows that the chemokine receptor 7 (ccR7) and its ligand ccL19 may regulate tumor dissemination, their role in SCCHN is not clearly defined. CCR7 has been shown to regulate integrins, which facilitate adhesion of cancer cells to and/or migration through the extracellular matrix (EcM). To investigate the relationship between ccR7 and integrin αvβ3 in metastatic SccHN, we used adhesion and migration assays, immunofluorescence staining and western blotting to determine whether integrin αvβ3 can be activated by ccL19 in the metastatic SccHN cell line PcI-37B, which was pre-incubated with ccL19 or the integrin αvβ3 inhibitor, IS201. Our results demonstrate that ccR7 favors PcI-37B cell adhesion and migration, induces reorganization of the actin cytoskeleton and induces integrin αvβ3 phosphorylation. The integrin αvβ3 inhibitor, IS201, blocked all of these effects. ccR7 and integrin αvβ3 expression significantly and positively correlated with tumor size, clinical stage and nodal metastasis. Taken together, our data indicate that ccR7 regulates cell adhesion and migration via integrin αvβ3 in metastatic SccHN. These results should provide the groundwork for new strategies aimed at preventing SccHN metastasis.

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“…The migration assay was performed in Transwell cell culture chambers (Corning Incorporated Life Sciences, Tewksbury, MA, USA), as reported previously, with some modifications (9). Polyvinylpyrrolidone-free polycarbonate (PVFP) filters (8.0 µm pore size; Nuclepore, Pleasanton, CA, USA) were pre-coated with 1 µg fibronectin (Asahi Technoglass Co., Tokyo, Japan) on the lower compartment.…”

Section: Fluorescence-activated Cell Sorting (Facs) Analysismentioning

confidence: 99%

Antitumor immune activity by chemokine CX3CL1 in an orthotopic implantation of lung cancer model in vivo

Kee

Arita

Shinohara

et al. 2012

Molecular and Clinical Oncology

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Abstract. Due to their chemoattractant properties stimulating the accumulation of infiltrating immune cells in tumors, chemokines are known to have antitumor effects. Fractalkine, a unique CX3C chemokine, is expressed in activated endothelial cells, while its receptor, CX3CR1, is expressed in cytolytic immune cells, such as natural killer cells, monocytes and some CD8 + T cells. The biological properties of cancer cells are affected by the implantation organ and differences in immune systems, requiring cancer implantation in orthotopic organs in an in vivo experiment. To develop new therapy strategies for lung cancer, an animal model reflecting the clinical features of lung cancer was previously established. This study aimed to determine whether CX3CL1-induced biological functions should be used for immune cell-based gene therapy of lung cancer in the orthotopic implantation model. An orthotopic intrapulmonary implantation of CX3CL1-stable expression in mouse lung cancer (LLC-CX3CL1) was performed to analyze growth. Results showed a significant decrease in tumor growth in the lung compared to the control cells (LLC-mock). Furthermore, the antitumor effects of CX3CL1 were derived from natural killer cell activities in the depletion experiment in vivo. Therefore, CX3CL1 has the potential of a useful therapeutic target in lung cancer.

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CCL21 promotes the migration and adhesion of highly lymph node metastatic human non-small cell lung cancer Lu-99 in vitro

Cited by 33 publications

References 19 publications

Paracrine Activation of Chemokine Receptor CCR9 Enhances The Invasiveness of Pancreatic Cancer Cells

Paracrine Activation of Chemokine Receptor CCR9 Enhances The Invasiveness of Pancreatic Cancer Cells

Chemokine receptor 7 promotes cell migration and adhesion in metastatic squamous cell carcinoma of the head and neck by activating integrin αvβ3

Antitumor immune activity by chemokine CX3CL1 in an orthotopic implantation of lung cancer model in vivo

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