scholarly journals Resolving Metabolic Heterogeneity in Experimental Models of the Tumor Microenvironment from a Stable Isotope Resolved Metabolomics Perspective

Metabolites ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 249
Author(s):  
Teresa W. -M. Fan ◽  
Richard M. Higashi ◽  
Yelena Chernayavskaya ◽  
Andrew N. Lane
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Stable Isotope ◽  
Cancer Cells ◽  
Metabolic Regulation ◽  
Model Systems ◽  
Lung Cancer Cells ◽  
In Vivo Model ◽  
Nutrient Competition ◽  
Advantages And Disadvantages

The tumor microenvironment (TME) comprises complex interactions of multiple cell types that determines cell behavior and metabolism such as nutrient competition and immune suppression. We discuss the various types of heterogeneity that exist in solid tumors, and the complications this invokes for studies of TME. As human subjects and in vivo model systems are complex and difficult to manipulate, simpler 3D model systems that are compatible with flexible experimental control are necessary for studying metabolic regulation in TME. Stable Isotope Resolved Metabolomics (SIRM) is a valuable tool for tracing metabolic networks in complex systems, but at present does not directly address heterogeneous metabolism at the individual cell level. We compare the advantages and disadvantages of different model systems for SIRM experiments, with a focus on lung cancer cells, their interactions with macrophages and T cells, and their response to modulators in the immune microenvironment. We describe the experimental set up, illustrate results from 3D cultures and co-cultures of lung cancer cells with human macrophages, and outline strategies to address the heterogeneous TME.

High CO2 tumor microenvironment confers chemoresistance in lung cancer cells

2017 ◽  
Author(s):  
Ryota Kikuchi ◽  
Takao Tsuji ◽  
Yuki Iwai ◽  
Hiroyuki Nakamura ◽  
Kazutetsu Aoshiba
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
High Co2

scholarly journals ATP promotes cell survival via regulation of cytosolic [Ca2+] and Bcl-2/Bax ratio in lung cancer cells

2016 ◽  
Vol 310 (2) ◽  
pp. C99-C114 ◽  
Author(s):  
Shanshan Song ◽  
Krista N. Jacobson ◽  
Kimberly M. McDermott ◽  
Sekhar P. Reddy ◽  
Anne E. Cress ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Intracellular Signaling ◽  
Airway Epithelial Cells ◽  
Lung Cancer Cells ◽  
Plateau Phase ◽  
Normal Cells ◽  
Cell Functions

Adenosine triphosphate (ATP) is a ubiquitous extracellular messenger elevated in the tumor microenvironment. ATP regulates cell functions by acting on purinergic receptors (P2X and P2Y) and activating a series of intracellular signaling pathways. We examined ATP-induced Ca2+ signaling and its effects on antiapoptotic (Bcl-2) and proapoptotic (Bax) proteins in normal human airway epithelial cells and lung cancer cells. Lung cancer cells exhibited two phases (transient and plateau phases) of increase in cytosolic [Ca2+] ([Ca2+]cyt) caused by ATP, while only the transient phase was observed in normal cells. Removal of extracellular Ca2+ eliminated the plateau phase increase of [Ca2+]cyt in lung cancer cells, indicating that the plateau phase of [Ca2+]cyt increase is due to Ca2+ influx. The distribution of P2X (P2X1-7) and P2Y (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11) receptors was different between lung cancer cells and normal cells. Proapoptotic P2X7 was nearly undetectable in lung cancer cells, which may explain why lung cancer cells showed decreased cytotoxicity when treated with high concentration of ATP. The Bcl-2/Bax ratio was increased in lung cancer cells following treatment with ATP; however, the antiapoptotic protein Bcl-2 demonstrated more sensitivity to ATP than proapoptotic protein Bax. Decreasing extracellular Ca2+ or chelating intracellular Ca2+ with BAPTA-AM significantly inhibited ATP-induced increase in Bcl-2/Bax ratio, indicating that a rise in [Ca2+]cyt through Ca2+ influx is the critical mediator for ATP-mediated increase in Bcl-2/Bax ratio. Therefore, despite high ATP levels in the tumor microenvironment, which would induce cell apoptosis in normal cells, the decreased P2X7 and elevated Bcl-2/Bax ratio in lung cancer cells may enable tumor cells to survive. Increasing the Bcl-2/Bax ratio by exposure to high extracellular ATP may, therefore, be an important selective pressure promoting transformation and cancer progression.

scholarly journals Study on metastasis inhibition of Kejinyan decoction on lung cancer by affecting tumor microenvironment

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Meijuan Chen ◽  
Cheng Hu ◽  
Qian Gao ◽  
Liqiu Li ◽  
Ziyu Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Flow Cytometry ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Tumor Tissue ◽  
Macrophage Polarization ◽  
Lung Cancer Cells ◽  
Inflammatory Factors ◽  
High Dose

Abstract Background Kejinyan decoction, as an experienced formula of Zhou Zhongying (the Master of Traditional Chinese Medicine) has been widely used in clinic for lung cancer treatment in China, while the anti-lung cancer mechanism of it is still remained to be elucidated. Herein, our basic study found that the survival of lung cancer xenograft mice was significantly prolonged after intragastrically administered high dose of Kejinyan decoction (3.8 g per kg BW) for 15 days. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. Thus in this study, we aim to elucidate the anti-metastasis effects of Kejinyan decoction. Methods RNA-Seq was used to find out the gene regulation of Kejinyan decoction on the mice, flow cytometry assay was used to detect the immunocytes in the spleen, ELISA assay was used to detect the inflammatory factors in the serum and spleen, and immunofluorescence assay was used to detect the level of immune cells and the expression of glycol-metabolism related enzymes in situ. Also, we established a lung cancer orthotopic xenograft tumor model to assess the influence of Kejinyan decoction on the metastatic ability of lung cancer cells in vivo. Results GO analysis of gene sequencing of tumor tissue samples showed that Kejinyan decoction regulated immune response. Further flow cytometry analysis of splenic lymphocyte showed that Kejinyan decoction upregulated M1 macrophages and downregulated M2 macrophages, while the total level of macrophages changed little, which was verified by detection of CD68, F4/80, CD206, and CD86 in tumor tissue section. Moreover, detection of inflammatory cytokines showed that Kejinyan decoction downregulated TNF-α, IFN-γ, IL-6, as well as IL-4, IL-13 in tumor microenvironment. Further studies also showed that Kejinyan decoction had little effect on tumor hypoxia, but downregulated glycolysis in tumor tissues. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. Conclusion Our findings conclude that Kejinyan decoction inhibited lung cancer cell metastasis through affecting macrophage polarization and energy reprogramming.

scholarly journals Fibronectin in the Tumor Microenvironment Activates a TLR4-dependent Inflammatory Response in Lung Cancer Cells

2020 ◽  
Vol 11 (11) ◽  
pp. 3099-3105
Author(s):  
Christina Cho ◽  
Carol Horzempa ◽  
Christine M. Longo ◽  
Donna M. Peters ◽  
David M. Jones ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Inflammatory Response ◽  
Cancer Cells ◽  
Lung Cancer Cells
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