Monocyte Chemoattractant Protein-1 Serum Levels in Patients with Breast Cancer

Lebrecht, Antje; Grimm, Christoph; Lantzsch, Tilmann; Ludwig, Elisabeth; Hefler, Lukas; Ulbrich, Eva; Koelbl, Heinz

doi:10.1159/000077718

Cited by 116 publications

(78 citation statements)

References 15 publications

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“…It requires binding of tumor cells to specific adhesion molecules on the surface of endothelial cells. Chemokines, such as monocyte chemoattractant protein-1 (MCP-1) (Lebrecht et al, 2004;Kuroda et al, 2005) and several adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) (Silva et al, 2006;Kobayashi et al, 2007), are involved in this process. It is striking to notice that MCP-1, VCAM-1 and ICAM-1 are classical inflammatory mediators which mediate transendothelial migration of leukocytes (Desideri and Ferri, 2005).…”

Section: Introductionmentioning

confidence: 99%

Oral administration of PCBs induces proinflammatory and prometastatic responses

Sipka

Eum

Son

et al. 2008

Environmental Toxicology and Pharmacology

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Exposure to specific congeners of polychlorinated biphenyls (PCBs) can induce proinflammatory alterations, which may contribute to the formation of blood-borne tumor metastasis. The main aim of the present study was to establish an experimental model of PCB exposure in which PCBs are administered by oral gavage, which resembles the human exposure through the food chain. To determine structure-function relationship, we studied induction of inflammatory responses in the livers, lungs and brains of mice treated with PCB77 (a major coplanar PCB), PCB104 (a non-coplanar PCB with multiple ortho-chlorine substituents), and PCB153 (a major non-coplanar PCB) after a single gavage dose (150 µmol/kg body weight). The strongest expression of proinflammatory proteins occurred 24 h following the PCB administration independent of the class of PCB congeners. These data indicate that food-chain exposure to PCBs can induce proinflammatory mediators in organs that are potential targets for PCB-induced toxicity.

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Section: Introductionmentioning

confidence: 99%

Oral administration of PCBs induces proinflammatory and prometastatic responses

Sipka

Eum

Son

et al. 2008

Environmental Toxicology and Pharmacology

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“…We have previously reported a trend toward higher levels of circulating MCP-1 in breast cancer patients compared to age-matched controls [18], with no significant correlation to commonly used prognostic indicators identified. A consensus has yet to be reached as to whether circulating MCP-1 is a positive or negative prognostic indicator in breast cancer patients [19,20].…”

Section: Introductionmentioning

confidence: 99%

Systemic chemokine levels in breast cancer patients and their relationship with circulating menstrual hormones

Potter

Dwyer

Curran

et al. 2008

Breast Cancer Res Treat

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Introduction The chemokines Stromal CellDerived Factor-1a (SDF-1a/CXCL12) and Monocyte Chemotactic Protein-1 (MCP-1/CCL2) have been implicated in breast cancer progression. We recently reported elevated systemic MCP-1 in breast cancer patients. This study investigated circulating levels of SDF-1a in breast cancer patients, and addressed potential hormonal regulation of these two potent chemokines. Methods SDF-1a levels were determined by ELISA in 114 breast cancer patients and 85 controls, and correlated with clinical data. Blood samples were collected from 36 healthy premenopausal volunteers weekly for four weeks to measure Luteinising Hormone (LH), Follicular Stimulating Hormone (FSH), Oestradiol and Progesterone using a Bayer ADVIA Ò Centaur Immunoassay system, in parallel with SDF-1a and MCP-1. CXCL12 expression was determined using RQ-PCR in primary tumour stromal cells (n = 16) harvested at surgery. Results Plasma SDF-1a was significantly higher in breast cancer patients than age-matched controls and had a significant correlation with tumour grade and epithelial subtype. Investigation of menstrual variations of these chemokines revealed lower SDF-1a levels in the mid-luteal phase of the menstrual cycle and a significant positive correlation with circulating Oestradiol. MCP-1 levels showed no correlation with menstrual hormones. There was a trend towards increased CXCL12 expression in tumour compared to normal stromal cells. Conclusions The elevated level of SDF-1a detected in breast cancer patients, and it's correlation with prognostic indicators, highlights the importance of this chemokine in disease progression. Elucidation of factors influencing chemokine secretion supports clarification of their role in tumourigenesis.Keywords Breast cancer Á Menstrual hormones Á Monocyte Chemotactic Protein-1 (MCP-1/CCL2) Á Prognosis Á Stromal Cell-derived Factor 1-a (SDF-1a/CXCL12)

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“…Over 50% of breast cancer tumor samples had intense staining of CCL2 in tumor cells (22). Prognostic analysis further revealed that high expression of CCL2 was correlated with advanced tumor stage, lymph node metastasis (23), and early relapse (24). CCL2 up-regulation in breast tumors was also associated with the infiltration of tissue-associated macrophages (TAMs) 3 and with increased microvessel density (22,24).…”

mentioning

confidence: 99%

Chemokine (C-C Motif) Ligand 2 Engages CCR2+ Stromal Cells of Monocytic Origin to Promote Breast Cancer Metastasis to Lung and Bone

Lü

Kang

2009

Journal of Biological Chemistry

230

181

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Metastatic spread of cancer to distant vital organs, including lung and bone, is the overwhelming cause of breast cancer mortality and morbidity. Effective treatment of systemic metastasis relies on the identification and functional characterization of metastasis mediators to multiple organs. Overexpression of the chemokine (C-C motif) ligand 2 (CCL2) is frequently associated with advanced tumor stage and metastatic relapse in breast cancer. However, the functional mechanism of CCL2 in promoting organ-specific metastasis of breast cancer has not been rigorously investigated. Here, we used organ-specific metastatic sublines of the MDA-MB-231 human breast cancer cell line to demonstrate that overexpression of CCL2 promotes breast cancer metastasis to both lung and bone. Conversely, blocking CCL2 function with a neutralizing antibody reduced lung and bone metastases. The enhancement of lung and bone metastases by CCL2 was associated with increased macrophage infiltration and osteoclast differentiation, respectively. By performing functional assays with primary cells isolated from the wild type, CCL2 and CCR2 knock-out mice, we showed that tumor cellderived CCL2 depends on its receptor CCR2 (chemokine, CC motif, receptor 2) expressed on stromal cells to exert its function in promoting macrophage recruitment and osteoclast differentiation. Overall, these data demonstrated that CCL2-expressing breast tumor cells engage CCR2 ؉ stromal cells of monocytic origin, including macrophages and preosteoclasts, to facilitate colonization in lung and bone. Therefore, CCL2 and CCR2 are promising therapeutic targets for simultaneously inhibiting lung and bone metastasis of breast cancer.Breast cancer is the most common malignancy in women in the United States, with an estimated 182,000 new cases and 40,000 deaths in 2008 (1). Late stage breast cancer patients develop metastases in bone, lung, liver, brain, and other organs, which are responsible for most breast cancer-related mortality and morbidity (2). Severe complications from bone metastasis include debilitating bone fractures, nerve compression and bone pain, and hypercalcemia (3-5), whereas lung metastasis is accompanied by cough, bloody sputum, rib cage pain, and, eventually, failure of the respiratory functions (6). Colonization of different secondary organs by breast cancer is believed to be a complex, multigenic process that depends on productive interactions between tumor cells and stromal microenvironments through concerted actions of organ-specific metastasis genes (7,8). Functional genomic analysis of preclinical models of breast cancer to bone, lung, and brain have identified distinct sets of organ-specific metastasis genes (9 -11), providing novel mechanistic insights into key rate-limiting steps of metastasis to different organs. However, as advanced breast cancer patients often suffer from metastases at several secondary organs, identifying genes that are capable of instigating metastasis to multiple sites may provide the ideal targets for therapeutic interventio...

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Monocyte Chemoattractant Protein-1 Serum Levels in Patients with Breast Cancer

Cited by 116 publications

References 15 publications

Oral administration of PCBs induces proinflammatory and prometastatic responses

Oral administration of PCBs induces proinflammatory and prometastatic responses

Systemic chemokine levels in breast cancer patients and their relationship with circulating menstrual hormones

Chemokine (C-C Motif) Ligand 2 Engages CCR2+ Stromal Cells of Monocytic Origin to Promote Breast Cancer Metastasis to Lung and Bone

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