A Central Role for Tumor-derived Monocyte Chemoattractant Protein-1 in Malignant Pleural Effusion

Stathopoulos, Georgios T.; Psallidas, Ioannis; Moustaki, Ardiana; Moschos, Charalampos; Kollintza, Androniki; Karabela, Sophia P.; Porfyridis, Ilias; Vassiliou, Spyridoula; Karatza, Marilena; Zhou, Zongmin; Joo, Myungsoo; Blackwell, Timothy S.; Roussos, Charis; Graf, Daniel; Kalomenidis, Ioannis

doi:10.1093/jnci/djn325

Cited by 86 publications

(172 citation statements)

References 38 publications

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“…It is known that MCP-1 secreted from tumor cells is an important determinant in the pathogenesis of human lung cancers. Previous studies have also demonstrated that blockade of MCP-1, as mediated by neutralizing antibodies, in several animal models of non-small cell lung cancer significantly slowed the growth of primary tumors (37,38). These results, thus, supported the notion that FMS could not only suppress the LLC1 cell growth but also attenuate relative inflammation levels in vivo.…”

Section: Fuc-enriched F3 Polysaccharide Fraction Induced Antibodies Rsupporting

confidence: 64%

Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes

Liao

Liang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Carbohydrate-based vaccines have shown therapeutic efficacy for infectious disease and cancer. The mushroom Ganoderma lucidum (Reishi) containing complex polysaccharides has been used as antitumor supplement, but the mechanism of immune response has rarely been studied. Here, we show that the mice immunized with a L-fucose (Fuc)-enriched Reishi polysaccharide fraction (designated as FMS) induce antibodies against murine Lewis lung carcinoma cells, with increased antibody-mediated cytotoxicity and reduced production of tumor-associated inflammatory mediators (in particular, monocyte chemoattractant protein-1). The mice showed a significant increase in the peritoneal B1 B-cell population, suggesting FMS-mediated anti-glycan IgM production. Furthermore, the glycan microarray analysis of FMS-induced antisera displayed a high specificity toward tumor-associated glycans, with the antigenic structure located in the nonreducing termini (i.e., Fucα1-2Galβ1-3GalNAc-R, where Gal, GalNAc, and R represent, respectively, Dgalactose, D-N-acetyl galactosamine, and reducing end), typically found in Globo H and related tumor antigens. The composition of FMS contains mainly the backbone of 1,4-mannan and 1,6-α-galactan and through the Fucα1-2Gal, Fucα1-3/4Man, Fucα1-4Xyl, and Fucα1-2Fuc linkages (where Man and Xyl represent D-mannose and D-xylose, respectively), underlying the molecular basis of the FMSinduced IgM antibodies against tumor-specific glycans. mushroom polysaccharide | antitumor activity | anti-Globo H antibody V arious forms of herbal medicine polysaccharides have become valuable as health supplements worldwide (1, 2), suggesting that administration of such polysaccharides may improve innate immunity in vivo. The underlying molecular mechanisms, however, still remain ambiguous. Aberrant terminal fucosylation as well as sialylation in tumor-associated glycans is one of several glycosylation events important in cancer progression (3, 4), and such unusual glycans have recently been used for the development of anticancer vaccines (5-7). As an example, the Globo H-based glycoconjugate vaccines are currently undergoing large-scale clinical trials and have shown promise in therapeutic treatment (8, 9). Studies on the immune response to pathogenic microorganisms (such as Haemophilus influenza type B and Streptococcus pneumonia) have demonstrated that polysaccharides containing repeating antigenic units are generally T cell-independent (TI) (10, 11). Furthermore, recent findings revealed that specific B-cell subsets could establish memory for providing specific Ig synthesis in response to TI-associated polysaccharides (12)(13)(14). In an attempt to understand the biological significance of polysaccharides derived from natural sources, we previously isolated and characterized a crude extract fraction of water-soluble and L-fucose (Fuc)-containing polysaccharides (F3) from Ganoderma lucidum (Reishi) (a mushroom that has been long used as a herb medicine) (15). F3 has since been shown essential for regulation of cytokine network...

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Section: Fuc-enriched F3 Polysaccharide Fraction Induced Antibodies Rsupporting

confidence: 64%

Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes

Liao

Liang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…For the first time, murine osteopontin functions during in vivo metastasis are linked with CCL2 signaling, a known druggable trait of thoracic tumor dissemination. [47][48][49][50] CCL2 can, in turn, enhance osteopontin signaling, since it augments the expression of the osteopontin receptor a v b 3 integrin. 51,52 Both molecules activate pathways such as FAK/Akt, MAPK, JAK2-Stat5, p38MAPK, and NF-kB in endothelial cells, thereby promoting adhesion, extravasation, and immune evasion of circulating tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

et al. 2016

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The lungs are ubiquitous receptacles of metastases originating from various bodily tumors. Although osteopontin (SPP1) has been associated with tumor dissemination, the role of its isoforms in lung-directed metastasis is incompletely understood. We employed syngeneic mouse models of spontaneous and induced lung-targeted metastasis in C57BL/6 mice competent and deficient in both Spp1 alleles. Tumorderived osteopontin expression was modulated using either stable anti-Spp1 RNA interference, or forced overexpression of intracellular and secreted Spp1 isoforms. Identified osteopontin's downstream partners were validated using lung adenocarcinoma cells conditionally lacking the Trp53 gene and Ccr2-deficient mice. We determined that host-derived osteopontin was dispensable for pulmonary colonization by different tumor types. Oppositely, tumor-originated intracellular osteopontin promoted tumor cell survival by preventing tumor-related protein 53-mediated apoptosis, while the secretory osteopontin functioned in a paracrine mode to accelerate lung metastasis by enhancing tumor-derived C-C-motif chemokine ligand 2 signaling to cognate host receptors. As new ways to target osteopontin signaling are becoming available, the cytokine may constitute an important therapeutic target against pulmonary involvement by cancers of other organs. KEYWORDSC-C-motif chemokine ligand 2; inflammation and cancer; secreted phosphoprotein 1; spontaneous lung metastasis; tumor-related protein 53

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“…The concentration of protein and lactate dehydrogenase (LDH) in MPE is a prognostically significant biochemical feature (8). In addition, numerous types of cytokine, including interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, IL-12, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) are detected in MPE (9)(10)(11)). An increased concentration of vascular endothelial growth factor (VEGF), which is mainly secreted from endothelial cells is also detected in MPE (12).…”

Section: Introductionmentioning

confidence: 99%

“…Since clinical features, biomedical features and numerous cytokines have been reported to be associated with MPE, and a single parameter may not serve as an optimal biomarker for predicting MPE (8)(9)(10)(11)(12)(13)(14)(15), the present study assessed whether a combination of biochemical features, clinical features and cytokine levels in pleural effusion may distinguish between BPE and MPE. The clinical and biochemical features of pleural effusion were determined and the concentration of cytokines in collected BPE and MPE samples was evaluated using cytometric bead arrays.…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor and protein level in pleural effusion for differentiating malignant from benign pleural effusion

Chang

Liu

et al. 2017

Oncology Letters

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Abstract. Pleural effusion is associated with multiple benign and malignant conditions. Currently no biomarkers differentiate malignant pleural effusion (MPE) and benign pleural effusion (BPE) sensitively and specifically. The present study identified a novel combination of biomarkers in pleural effusion for differentiating MPE from BPE by enrolling 75 patients, 34 with BPE and 41 with MPE. The levels of lactate dehydrogenase, glucose, protein, and total cell, neutrophil, monocyte and lymphocyte counts in the pleural effusion were measured. The concentrations of interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-α, interferon γ, transforming growth factor-β1, colony stimulating factor 2, monocyte chemoattractant protein-1 and vascular endothelial growth factor (VEGF) were detected using cytometric bead arrays. Protein and VEGF levels differed significantly between patients with BPE and those with MPE. The optimal cutoff value of VEGF and protein was 214 pg/ml and 3.35 g/dl respectively, according to the receiver operating characteristic curve. A combination of VEGF >214 pg/ml and protein >3.35 g/dl in pleural effusion presented a sensitivity of 92.6% and an accuracy of 78.6% for MPE, but was not associated with a decreased survival rate. These results suggested that this novel combination strategy may provide useful biomarkers for predicting MPE and facilitating early diagnosis.

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A Central Role for Tumor-derived Monocyte Chemoattractant Protein-1 in Malignant Pleural Effusion

Abstract: MCP-1 produced by tumor cells is an important determinant of their capacity to induce the formation of MPE and may be a useful target for the treatment of malignant pleural disease.

Cited by 86 publications

References 38 publications

Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes

Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes

Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis

Vascular endothelial growth factor and protein level in pleural effusion for differentiating malignant from benign pleural effusion

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