Paracrine Suppression of VEGF Secretion by Erythropoietin Inhibits Tumor Growth.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3909-3909
Author(s):  
Carroll R. Smith ◽  
Kenneth J. Salleng ◽  
Vaia Y. Sigounas ◽  
Adam Asch ◽  
George Sigounas
Keyword(s):  
Tumor Growth ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Lung Metastases ◽  
Control Group ◽  
Lewis Lung ◽  
Average Volume ◽  
Primary Tumors ◽  
Significant Difference

Abstract Several studies have reported that erythropoietin (Epo) is a pleiotropic cytokine with biological properties in addition to its primary function in regulating maturation, growth and survival along the erythroid lineage. Recently, a number of investigators have reported that various neoplastic tissues and human cancer cell lines express Epo and the Epo receptor (EpoR), raising suspicion for the presence of an autocrine-paracrine Epo-EpoR system. It has been shown that inhibition of vascular endothelial growth factor (VEGF) results in an increase of Epo secretion and increased hematocrit in vivo. In this study, we used an in vivo Lewis lung carcinoma model to examine a converse Epo effect on VEGF production and metastasis. Lewis lung carcinoma (LLC) cells were injected subcutaneously into C57BL mice. The plasma levels of VEGF, the tumor vessel formation, the size of the primary tumors and the extent of lung metastatic disease were determined. In addition, intravenously injected LLC cells seeded in the lungs were assessed. Tumor-bearing animals treated with Epo had 23.6% less VEGF in the plasma compared to saline treated mice (p<0.04). There was no correlation between VEGF concentration and hemoglobin levels in either group of animals. Tumor sections indicated that the number of blood vessels was higher (10.7% for inner and 23.8% for outer, respectively) in tumors obtained from animals treated with saline compared to Epo-treated mice (p>0.05). Using non-parametric analysis, we found that there was a statistically significant difference in tumor growth between saline-treated and Epo-treated animals (p<0.05). However, the number of lung metastases derived from primary tumors was similar in both groups. In assessing size of the metastatic tumors, we found that the average volume of lung nodules was 24.2% higher in saline-injected animals compared to Epo-treated mice. The number of tumors seeded in the lungs following intravenous injection of LLC cells was similar in animals treated with a high dosage of Epo, low dosage of Epo or saline. In addition, the average volume of the nodules was reduced by 42% in animals treated with high and low concentrations of Epo compared to the control group (p = 0.03). In conclusion, Epo exerts a paracrine suppressive effect on VEGF secretion resulting in slower tumor growth in this model.

scholarly journals ATIQCTPC targeting MMP-9: a key step to slowing primary tumor growth and inhibiting metastasis of lewis lung carcinoma in vivo

Oncotarget ◽  
2017 ◽  
Vol 8 (38) ◽  
pp. 63881-63889 ◽  
Author(s):  
Yuji Wang ◽  
Xinyi Xu ◽  
Ce Song ◽  
Jianhui Wu ◽  
Xi Hu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Lung Carcinoma ◽  
Primary Tumor ◽  
Lewis Lung Carcinoma ◽  
Lewis Lung ◽  
Primary Tumor Growth

In Vitro and in Vivo Selection of two Lewis Lung Carcinoma Cell Lines

1979 ◽  
Vol 65 (6) ◽  
pp. 657-664 ◽  
Author(s):  
Ada Sacchi ◽  
Anna Corsi ◽  
Marco Caputo ◽  
Gabriella Zupi
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Lung Metastases ◽  
Tumor Cell Lines ◽  
Lewis Lung ◽  
Selection Of

Two tumor cell lines adapted to grow in vitro were originated from an explant of lung metastases of Lewis lung carcinoma. These lines differ in their malignancy when reinoculated into syngeneic animals; nevertheless, they do not show any difference for their in vitro clonogenic ability. From these lines 2 in vivo sublines of 3LL carcinoma were developed. The TD 50 of the 2 in vivo sublines are different, and both the values obtained are lower than that of the original line. These results are interpreted as a selection of more malignant tumor cell lines.

scholarly journals Effects of Sevoflurane on Lewis Lung Carcinoma Cell Proliferation In Vivo and In Vitro

Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 45
Author(s):  
Yeojung Kim ◽  
Sangwon Yun ◽  
Keun-A Shin ◽  
Woosuk Chung ◽  
Youngkwon Ko ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Carcinoma ◽  
Tumor Size ◽  
Lewis Lung Carcinoma ◽  
In Vitro Study ◽  
Control Group ◽  
Lewis Lung ◽  
And Control

Background and objectives: There are several studies that sevoflurane could enhance proliferation of cancer cells, while others suggest no effect on clinical outcome. We conducted in vivo and in vitro experiments to investigate the effects of sevoflurane, a volatile anesthetic, on proliferation and outcomes of Lewis lung carcinoma (LLC) cells. Materials and Methods: A total of 37 mice were injected with LLC cells to compare the tumor size and survival of the sevoflurane exposed group (sevo group) and control group. The sevo group was exposed to 2% sevoflurane and 4 L/min of oxygen for 1 h per day 3 times per week, and the control group was exposed only to 4 L/min of oxygen. In vitro study, 12 plates incubated with LCC cells. 6 plates were exposed to 2% sevoflurane for 1 hr/day for 3 days and 6 plates were not exposed, and cell proliferation was compared after 3 days. Results: There were no significant differences in survival or tumor size between mice exposed to sevoflurane and control mice (survival: 29.06 ± 4.45 vs. 28.76 ± 3.75, p = 0.836; tumor size: 0.75 (0.41–1.02) vs. 0.49 (0.11–0.79), p = 0.153). However, in vitro study, the proliferation of LLC cells exposed to sevoflurane increased by 9.2% compared to the control group (p = 0.018). Conclusions: Sevoflurane (2 vol%) exposure could promote proliferation of LLC cells in vitro environment, but may not affect proliferation of LLC cells in vivo environment. These results suggest that in vitro studies on the effects of anesthetics on cancer may differ from those of in vivo or clinical studies.

scholarly journals Treatment of Lewis lung carcinoma by photodynamic therapy and glucan from barley

Medicina ◽  
2009 ◽  
Vol 45 (6) ◽  
pp. 480 ◽  
Author(s):  
Dalia Akramienė ◽  
Gražina Graželienė ◽  
Janina Didžiapetrienė ◽  
Egidijus Kėvelaitis
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Specific Interaction ◽  
Control Group ◽  
Complement Receptor ◽  
Lewis Lung ◽  
Complement Receptor 3

Objective. During the photodynamic treatment, complement system is activated and tumor cells are opsonized with iC3b fragment. β-glucans can enhance cytotoxicity of iC3bopsonized cells due to their specific interaction with complement receptor 3 (CR3; CD11b/CD18) on the surface of the effector cells. In contrast to microorganisms, tumor cells lack β-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism could be induced in the presence of β-glucans. This study aimed at determining the influence of coadministration of β-glucan from barley on the efficacy of photodynamic tumor therapy (PDT). Material and methods. C57 Bl/6 female mice bearing Lewis lung carcinoma were used throughout the study. Mice were randomized into groups (15 in each group) and exposed to the treatment with intravenous Photofrin injection (dose, 10 mg/kg) and after 24 h following laser illumination, or with oral administration of β-glucan from barley at a dose of 400 μg/mouse per day up to 5 days, or with their combination. Tumor growth dynamics and survival of the treated and untreated mice were monitored. Results. Tumor volume in all treated groups was significantly lower (P<0.001) than that in the control group. The most effective tumor growth suppression (P=0.033) was achieved in mice treated with combination of PDT and β-glucan from barley as compared with PDT alone. The best survival was achieved in the same group, but difference was not significant as compared to the control group (P=0.143) and to PDT alone group (P=0.319). Conclusions. The present study demonstrates that coadministration of β-glucan from barley can enhance efficacy of photodynamic therapy.

scholarly journals EFFECT OF DICHLOROACETATE ON LEWIS LUNG CARCINOMA GROWTH AND METASTASIS

2015 ◽  
Vol 37 (2) ◽  
pp. 126-129 ◽  
Author(s):  
D L Kolesnik ◽  
O N Pyaskovskaya ◽  
I V Boychuk ◽  
O I Dasyukevich ◽  
O R Melnikov ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Tumor Tissue ◽  
Control Group ◽  
Lewis Lung ◽  
Antimetastatic Activity ◽  
Apoptosis Level

A hallmark of malignancy is excessive tumor glycolysis, even in the presence of oxygen, which causes lactacidosis in the tumor microenvironment and favors tumor cell proliferation and survival. For this reason antimetabolic agents which target tumor cell metabolism are being researched extensively as promising anticancer drugs. Aim: To study the effect of lactacidosis on survival of Lewis lung carcinoma (LLC) cells at the conditions of nutritional substrate deficiency in vitro and evaluate antitumor and antimetastatic activity against LLC/ R9 in vivo. Materials and Methods: LLC variant LLC/R9 was used as experimental tumor model. Tumor cell viability was determined using trypan blue staining. Apoptosis level was counted with the use of Hoechst 33258 dye. Lactate content in the tumor tissue was evaluated by enzyme method with the use of lactate dehydrogenase. Reactive oxygen species was determined using 2.7-dichlorofluorescein diacetate. Effects of dichloroacetate (DCA) on the growth and metastasis of LLC/R9 were analyzed by routine procedures. Evaluation of DCA effect toward electron-transport chain (ETC) components was performed using EPR. Results: It has been shown that at the conditions of lactacidosis and glucose deficiency, LLC/R9 cell viability in vitro was higher by 30% (р < 0.05) and apoptosis level was triply lower (р < 0.05) than these indices at the conditions of glucose deficiency only. In mice with transplanted LLC/R9 tumors treated for 3 weeks per os with DCA at the total dose of 1.5 g/kg of body weight starting from the next day after tumor transplantation, the primary tumor volume was just by 30% lower than that in control group. At the same time, the number and volume of lung metastases in animals treated with DCA were by 59% (р < 0.05) and 94% (р < 0.05) lower, respectively, than these indices in the control group. DCA treatment resulted in nearly 30% increase (р < 0.05) of lactate content in tumor tissue compared to that in the control, but did not affect significantly the levels of heme iron complexes with NO (at gmed = 2.007) in mitochondrial ETC proteins and Fe-S cluster proteins (at g = 1.94) in tumor cells. Conclusions: It has been shown that lactacidosis significantly promoted LLC/R9 cell survival at the conditions of glucose deficiency in vitro. If LLC/R9 developed in vivo, DCA as the compound with antilactacidosis activity did not suppress significantly the primary tumor growth but exerted significant antimetastatic activity.

scholarly journals Human Biofield Therapy Modulates Tumor Microenvironment and Cancer Stemness in Mouse Lung Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153473542094039
Author(s):  
Peiying Yang ◽  
Patrea R. Rhea ◽  
Tara Conway ◽  
Sita Nookala ◽  
Venkatesh Hegde ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Fold Increase ◽  
Stem Cell Marker ◽  
Control Group ◽  
M2 Macrophages ◽  
Lewis Lung ◽  
Biofield Therapy

Studies have demonstrated that purported biofield therapy emitted from humans can inhibit the proliferation of cancer cells and suppress tumor growth in various cancers. We explored the effects of biofield therapy on tumor growth in the Lewis lung carcinoma and expanded mechanistic outcomes. We found biofield therapy did not inhibit tumor growth. However, the experimental (Ex) condition exposed tumors had a significantly higher percentage of necrosis (24.4 ± 6.8%) compared with that of the Control condition (6.5 ± 2.7%; P < .02) and cleaved caspase-3 positive cells were almost 2.3-fold higher ( P < .05). Similarly, tumor-infiltrating lymphocytes profiling showed that CD8+/CD45+ immune cell population was significantly increased by 2.7-fold in Ex condition ( P < .01) whereas the number of intratumoral FoxP3+/CD4+ (T-reg cells) was 30.4% lower than that of the Control group ( P = .01), leading to a significant 3.1-fold increase in the ratio of CD8+/T-reg cells ( P < .01). Additionally, there was a 51% lower level of strongly stained CD68+ cells ( P < .01), 57.9% lower level of F4/80high/CD206+ (M2 macrophages; P < .02) and a significant 1.8-fold increase of the ratio of M1/M2 macrophages ( P < .02). Furthermore, Ex exposure resulted in a 15% reduction of stem cell marker CD44 and a significant 33% reduction of SOX2 compared with that of the Controls ( P < .02). The Ex group also engaged in almost 50% less movement throughout the session than the Controls. These findings suggest that exposure to purported biofields from a human is capable of enhancing cancer cell death, in part mediated through modification of the tumor microenvironment and stemness of tumor cells in mouse Lewis lung carcinoma model. Future research should focus on defining the optimal treatment duration, replication with different biofield therapists, and exploring the mechanisms of action.

scholarly journals Extracellular vesicles-released parathyroid hormone-related protein from Lewis lung carcinoma induces lipolysis and adipose tissue browning in cancer cachexia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenjun Hu ◽  
Hairong Xiong ◽  
Zeyuan Ru ◽  
Yan Zhao ◽  
Yali Zhou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Parathyroid Hormone ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Cancer Cachexia ◽  
Lewis Lung ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Tissue Browning

AbstractCancer cachexia is a metabolic disorder characterized by skeletal muscle wasting and white adipose tissue browning. Specific functions of several hormones, growth factors, and cytokines derived from tumors can trigger cachexia. Moreover, adipose tissue lipolysis might explain weight loss that occurs owing to cachexia. Extracellular vesicles (EVs) are involved in intercellular communication. However, whether EVs participate in lipolysis induced by cancer cachexia has not been thoroughly investigated. Using Lewis lung carcinoma (LLC) cell culture, we tested whether LLC cell-derived EVs can induce lipolysis in 3T3-L1 adipocytes. EVs derived from LLC cells were isolated and characterized biochemically and biophysically. Western blotting and glycerol assay were used to study lipolysis. LLC cell-derived EVs induced lipolysis in vivo and vitro. EVs fused directly with target 3T3-L1 adipocytes and transferred parathyroid hormone-related protein (PTHrP), activating the PKA signaling pathway in 3T3-L1 adipocytes. Blocking PTHrP activity in LLC-EVs using a neutralizing antibody and by knocking down PTHR expression prevented lipolysis in adipocytes. Inhibiting the PKA signaling pathway also prevents the lipolytic effects of EVs. In vivo, suppression of LLC-EVs release by knocking down Rab27A alleviated white adipose tissue browning and lipolysis. Our data showed that LLC cell-derived EVs induced adipocyte lipolysis via the extracellular PTHrP-mediated PKA pathway. Our data demonstrate that LLC-EVs induce lipolysis in vitro and vivo by delivering PTHrP, which interacts with PTHR. The lipolytic effect of LLC-EVs was abrogated by PTHR knockdown and treatment with a neutralizing anti-PTHrP antibody. Together, these data show that LLC-EV-induced lipolysis is mediated by extracellular PTHrP. These findings suggest a novel mechanism of lipid droplet loss and identify a potential therapeutic strategy for cancer cachexia.

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