Predictive and prognostic value of LPS-stimulated cytokine secretion in metastatic non-small cell lung cancer

Vlachostergios, Panagiotis J.; Gioulbasanis, Ioannis; Ghosh, Sunita; Tsatsanis, Christos; Papatsibas, George; Xyrafas, A.; Hatzidaki, Eleana; Vasiliou, C.; Kamposioras, Konstantinos; Agelaki, Sofia; Margioris, Andrew N.; Nasi, Davide; Georgoulias, Vassilis; Papandreou, Christos N.

doi:10.1007/s12094-013-1021-5

Cited by 9 publications

(16 citation statements)

References 26 publications

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“…Elevated serum levels of IL‐6 have been associated with decreased survival, increased risk of post‐operative metastatic recurrence and poor chemo‐responsiveness . Elevated IL‐6 production following LPS stimulation of ex‐vivo peripheral blood samples in metastatic NSCLC patients is significantly associated with worsened progression‐free survival and overall survival . Additionally, high NSCLC STAT‐3 and phospho‐STAT3 staining, a downstream IL‐6 transcription factor, is a poor prognostic indicator for NSCLC patients …”

Section: Discussionmentioning

confidence: 99%

Gram-positive pneumonia augments non-small cell lung cancer metastasisviahost toll-like receptor 2 activation

et al. 2017

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Surgical resection of early stage nonsmall cell lung cancer (NSCLC) is necessary for cure. However, rates of postoperative bacterial pneumonias remain high and may confer an increased risk for metastasis. Toll-like receptors (TLRs) mediate the inflammatory cascade by recognizing microbial products at the surface of numerous cell types in the lung; however, little is known about how host TLRs influence NSCLC metastasis. TLR2 recognizes gram-positive bacterial cell wall components activating innate immunity. We demonstrate that lower respiratory tract infection with Streptococcus pneumonia augments the formation of murine H59 NSCLC liver metastases in C57BL/6 mice through host TLR2 activation. Infected mice demonstrate increased H59 and human A549 NSCLC adhesion to hepatic sinusoids in vivo compared with noninfected controls, a response that is significantly diminished in TLR2 knock-out mice. Intra-tracheal injection of purified TLR2 ligand lipoteichoic acid into mice similarly augments in vivo adhesion of H59 cells to hepatic sinusoids. Additionally, H59 and A549 NSCLC cells incubated with bronchoepithelial conditioned media show increased cell adhesion to extracellular matrix components in vitro and hepatic sinusoids in vivo in a manner that is dependent on bronchoepithelial TLR2 activation and interleukin-6 secretion. TLR2 is therefore a potential therapeutic target for gram-positive pneumonia-driven NSCLC metastasis.

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Section: Discussionmentioning

confidence: 99%

Gram-positive pneumonia augments non-small cell lung cancer metastasisviahost toll-like receptor 2 activation

et al. 2017

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“…8 The potential use of bacteria or endotoxins of the effects of anti-tumor has been widely researched for decades. 9 Although now LPS is not used to treat cancer due to its toxicities, the underlying theory was right has been revealed by the accumulating evidence 10,11 One experiment has verified that the cancer cell survival can be inhibited by LPS. 12 Functional studies show that LPS reduces cancer survival, invasion, and proliferation via various mechanisms, suggesting that LPS is an effective cancer progression management strategy.…”

Section: Introductionmentioning

confidence: 99%

<p>LPS Enhances the Chemosensitivity of Oxaliplatin in HT29 Cells via GSDMD-Mediated Pyroptosis</p>

Liu

Wang

et al. 2020

CMAR

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Introduction: Pyroptosis induced by lipopolysaccharide (LPS) is a dissolved form of cell death. The molecular marker gasdermin D, specifically GSDMD-N, is critically required for the induction of pyroptosis. Recently, there have been studies showing that LPS is closely related to tumor biology. Methods: Specimens from 40 patients with colorectal cancer (CRC) were collected. Eight-to twelve-week-old C57BL6 male mice (n=30) were raised. Immunohistochemistry and Western blot were performed to test the expression of GSDMD. Moreover, cytotoxicity assay, IL-18 and IL-1β ELISA, Annexin V and PI stain, and wound healing assay were also made. Gene Expression Profiling Interactive Analysis (GEPIA) was used to verify the expression of GSDMD and overall survival of CRC patients with a high/low expression of GSDMD. Results: In the research, we showed that the poor prognosis in CRC patients was significantly related to the GSDMD expression and significantly down-regulated in human colorectal cancer (CRC) tissues. Treatment with LPS, but not TNF-α, induced pyroptosis via promoting the expression of GSDMD and GSDMD-N membrane translocation and enhanced chemosensitivity in response to L-OHP in HT29 cells. Furthermore, the enforced expression of GSDMD in HT29 cells reduced cell survival and induced cell death. Discussion: These results of studies suggest that the low expression of GSDMD correlates with a poor CRC prognosis, and that pyroptosis induced by LPS may improve the anti-cancer effect of L-OHP, inhibiting the tumorigenesis of CRC by activating GSDMD. Our findings lay the foundation for further development of GSDMD serving as an important prognostic biomarker and a valid CRC therapeutic target.

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“…LPS serves not only as a physical barrier to keep bacteria from invading the outside environment, but also as a biomarker for the immune system to identify pathogenic bacteria, playing a key role in the inflammatory immune response and endotoxic shock . Endotoxins released by bacteria can affect the proliferation of A549 cells in vitro, and LPS can strongly induce NSCLC cell proliferation in many animal models …”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16] Endotoxins released by bacteria can affect the proliferation of A549 cells in vitro, and LPS can strongly induce NSCLC cell proliferation in many animal models. [17][18][19] In recent years, with the continuous development of traditional Chinese medicine (TCM), the national investment in TCM research has gradually increased and the anticancer role and underlying mechanisms of TCM have been elucidated to a certain extent. Active ingredients and natural Chinese herbal medicines play an important role in improving immune function, inhibiting cell proliferation and migration, promoting cell apoptosis, alleviating clinical symptoms, alleviating toxicity and the side effects of radiotherapy and chemotherapy, prolonging survival, reducing recurrence, and improving quality of life.…”

Section: Introductionmentioning

confidence: 99%

Hydroxysafflor yellow A inhibited lipopolysaccharide‐induced non‐small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

Jiang

Zhou

et al. 2019

Thoracic Cancer

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Background Chronic inflammation plays a significant role in the occurrence and development of non‐small cell lung cancer (NSCLC). Hydroxysafflor yellow A (HSYA), a chemical compound of the yellow color pigments extracted from the safflower, has been widely used in clinical treatment with positive antioxidation, anti‐inflammation, and antitumor effects. However, the role and underlying mechanisms of HYSA on development and progress in inflammation‐mediated NSCLC are unknown. Methods Cell counting kit‐8, colony formation, EdU, cell apoptosis, wound healing, Transwell migration and invasion, and enzyme‐linked immunosorbent assays; flow cytometry; and Western blotting were conducted using human NSCLC cell lines A549 and H1299. Results Lipopolysaccharide (LPS) significantly promoted the proliferation and enhanced colony formation of A549 and H1299 cells, while HYSA notably reversed the effects of LPS. HYSA induced apoptosis of LPS‐mediated A549 and H1299 cells in a dose dependent manner; and remarkably suppressed migration, invasion, and epithelial–mesenchymal transition (EMT), significantly regulated production of LPS‐induced inflammation cytokines, and downregulated protein expression of PI3K/Akt/mTOR and ERK/MAPK signaling pathways in LPS‐induced A549 and H1299 cells. Furthermore, PI3K (LY294002) and ERK (SCH772984) inhibitors remarkably inhibited proliferation, migration, invasion, and EMT, and induced apoptosis in LPS‐mediated A549 and H1299 cells. These effects were even more obvious in the presence of HYSA and LY294002 or SCH772984 compared to those of either agent alone. Conclusion HYSA suppressed LPS‐mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation‐mediated NSCLC.

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Predictive and prognostic value of LPS-stimulated cytokine secretion in metastatic non-small cell lung cancer

Abstract: The extent of IL-6 and IL-8 stimulation after ex vivo induction with LPS is an important predictor of clinical outcome in metastatic NSCLC patients.

Cited by 9 publications

References 26 publications

Gram-positive pneumonia augments non-small cell lung cancer metastasisviahost toll-like receptor 2 activation

Gram-positive pneumonia augments non-small cell lung cancer metastasisviahost toll-like receptor 2 activation

<p>LPS Enhances the Chemosensitivity of Oxaliplatin in HT29 Cells via GSDMD-Mediated Pyroptosis</p>

Hydroxysafflor yellow A inhibited lipopolysaccharide‐induced non‐small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

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