Tumor growth promoting activity of an immunosuppressive substance and its modulation by protein-bound polysaccharide PSK

1987 ◽  
Vol 15 (4) ◽  
pp. 347-351 ◽  
Author(s):  
Masahiko Fujii ◽  
Takayoshi Fujii ◽  
Ken Saito ◽  
Norio Takahashi ◽  
Chikao Yoshikumi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Immunosuppressive Substance ◽  
Growth Promoting

Tumor Growth-Promoting Effect of Immunosuppressive Substance in Mice

1989 ◽  
Vol 7 (4) ◽  
pp. 333-338
Author(s):  
Masahiko Fujii ◽  
Norio Takahashi ◽  
Takayoshi Fujii ◽  
Haruhisa Hayashi ◽  
Kenichi Matsunaga ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Promoting Effect ◽  
Immunosuppressive Substance ◽  
Growth Promoting

scholarly journals Tumor-growth–promoting cyclooxygenase-2 prostaglandin E2 pathway provides medulloblastoma therapeutic targets

2008 ◽  
Vol 10 (5) ◽  
pp. 661-674 ◽  
Author(s):  
Ninib Baryawno ◽  
Baldur Sveinbjörnsson ◽  
Staffan Eksborg ◽  
Abiel Orrego ◽  
Lova Segerström ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Prostaglandin E2 ◽  
Therapeutic Targets ◽  
Cyclooxygenase 2 ◽  
Growth Promoting

The Mechanism of Transfusion-Related Immunomodulation Is Related to the Transfusion of Dendritic Cells Expressing the CD200 (OX-2) Tolerance Signal and Alloantigen: Evidence from a Murine Tumor Model.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 831-831
Author(s):  
Morris A. Blajchman ◽  
Reginald M. Gorczynski ◽  
David A. Clark
Keyword(s):  
Dendritic Cells ◽  
Blood Transfusion ◽  
Tumor Growth ◽  
Pulmonary Nodules ◽  
Suppressor Cells ◽  
Tumor Model ◽  
Allogeneic Blood ◽  
Promoting Effect ◽  
Growth Promoting ◽  
Resistance To Infection

Abstract Background: The transfusion of blood products containing allogeneic leukocytes can alter recipient resistance to infection and stimulate the growth of some types of tumors in animal models of transfusion-induced tumor growth. Transfusion related immunomodulation (TRIM) represents a credible mechanism for the altered resistance to infection seen clinically, but cannot explain the growth of non-immunogenic tumors in syngeneic hosts seen regularly in the various transfusion-related animal models of tumor growth. Methods and Results: In this study the transfusion of 50–200 μL of unmodified anticoagulated allogeneic BALB/c (H-2d) mouse blood into C57B1/6 (H-2b) mice, four days before being intravenously injected with syngeneic (H-2b) FSL10 fibrosarcoma cells (1–2 x 106 cells per mouse) resulted in a significant increase in the number of pulmonary nodules observed at 3 weeks compared to that seen in control mice. The median number of pulmonary nodules increased in an allogeneic blood transfusion dose-dependent manner, as did the proportion of mice without pulmonary nodules. This tumor growth-promoting effect of the allogeneic blood transfusions required the presence in the transfused blood of allogeneic CD11c+ dendritic cells bearing the CD200 co-stimulatory tolerance signal. This tumor growth-promoting effect of allogeneic blood could be blocked by specific monoclonal antibodies to either CD11c or to CD200. CD200 receptor-mediated signaling alone, in the absence of alloantigen, failed to augment the number of TRIM-induced pulmonary tumor nodules. Physiological concentrations of TGFβ, but not IL-10, were shown to stimulate proliferation of FSL10 cells in vitro in these studies. In this context, it is known that CD200 together with alloantigens are known to stimulate development of suppressor cells acting via IL-10 and TGFβ in vivo. Allogeneic blood also caused a significant CD200-dependent accumulation of TGFβ+ suppressor cells in the spleen, 12 days after transfusion, when the spleen cells could be shown to adoptively transfer the TRIM effect to naive animals. Conclusions: These data support the hypothesis that allogeneic transfusions in an allogeneic blood transfusion mouse tumor model results in tumor growth promotion in recipient mice. This effect appears to result in both the induction of TGFβ-producing suppressor cells as well as requiring the transfusion of allogeneic CD11c+ dendritic cells, bearing both CD200 tolerance signaling molecules and alloantigens.

μ Opioid Receptor Stimulates a Growth Promoting and Pro-Angiogenic Tumor Microenvironment by Transactivating VEGF Receptor-2/Flk-1.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3687-3687
Author(s):  
Elliot J. Stephenson ◽  
Humberto J. Martinez-Suarez ◽  
Mariya Farooqui ◽  
Debabrata Mukhopadhyay ◽  
Deborah A. Hughes ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Opioid Receptor ◽  
Calcium Release ◽  
Small Gtpase ◽  
Endothelial Cell Proliferation ◽  
Vegf Receptor ◽  
Growth Promoting ◽  
Stimulation Of

Abstract Like VEGF, morphine stimulates MAPK/ERK and Akt, leading to the promotion of angiogenesis via NO dependent signaling (Cancer Res62: 4491, 2002). Morphine acts via pertussis toxin (PT)-dependent G-protein coupled receptors (GPCRS), while VEGF acts via receptor tyrosine kinases (RTKs). We showed that PT-dependent GPCRs transactivate VEGF receptor-2/Flk1 via small GTPase RhoA (JBC277: 4679, 2002; JBC278:20738, 2003). Therefore, we hypothesized that morphine via the mu opioid receptor (MOR) transactivates Flk1 and promotes a pro-angiogenic microenvironment. Morphine-induced proliferation of human umbilical vein endothelial cells (HUVEC) was completely abrogated by Y-27632 (100 μM), a highly selective and potent inhibitor of Rho-associated protein kinases, suggesting the activation of Rho signaling by morphine. Addition of 1 μM morphine potentiated VEGF-induced (10 ng/ml) proliferation of HUVEC by 25%. We observed a 30% increase in intracellular calcium release after VEGF stimulation of HUVEC pre-incubated with morphine as compared to HUVEC pre-incubated with PBS, detected by a change in the fluorescence ratio of the Fura-2 AM dye. These findings show that morphine, via MOR and Rho signaling, transactivates Flk1 leading to the stimulation of calcium signaling and endothelial cell proliferation. To functionally corroborate our hypothesis, we used MOR knockout (MOR-KO) mice and injected them with MOR-replete T241 fibrosarcoma cells. T241 fibrosarcoma tumor growth in vivo showed appearance of palpable and measurable tumors 2 days earlier in wild type (wt) as compared to MOR-KO mice. Tumor growth and angiogenesis were decreased by 20–35% in MOR-KO mice as compared to wt littermates during 3 weeks of tumor growth. None of the MOR-KO showed signs of lung metastasis versus 40% wt mice with metastasis. Morphine (1.42 for the first 2 wks and 2.14 mg/Kg/day later, respectively) stimulated 20–35% tumor growth in wt, but not in MOR-KO mice. Western immunoblotting showed a 10-fold increase in the expression of phospho-Flk1 in morphine treated wt tumors as compared to PBS-treated wt mice. Morphine did not stimulate phospho-Flk1 expression in MOR-KO mice. Western analysis of immunoprecipitates obtained with α-MOR antibody showed the expression of Flk1 and phospho-Flk1 in wt, but were not expressed in MOR-KO tumors. Thus, MOR stimulates the transactivation of Flk1 in wt mice but not in MOR-KO. These in vitro and in vivo data using MOR-KO mice and the MOR agonist, morphine, show that MOR stimulates endothelial proliferation, angiogenesis and promotes tumor growth and metastasis directly as well as by transactivating Flk1 phosphorylation. We speculate that MOR is a critical component of the ‘angiogenic switch’, which regulates the pro-angiogenic and growth promoting tumor microenvironment. Thus, MOR provides a novel target for developing anti-angiogenic therapies.

scholarly journals Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression

2020 ◽  
Vol 21 (11) ◽  
pp. 3990 ◽  
Author(s):  
Juliana H. Azambuja ◽  
Nils Ludwig ◽  
Saigopalakrishna S. Yerneni ◽  
Elizandra Braganhol ◽  
Theresa L. Whiteside
Keyword(s):  
Tumor Growth ◽  
In Vitro Model ◽  
Potential Therapeutic Target ◽  
Tumor Cell Migration ◽  
Arginase 1 ◽  
Growth Promoting ◽  
Vitro Model ◽  
Cell Migration And Proliferation

Interactions between tumor cells and tumor-associated macrophages (TAMs) are critical for glioblastoma progression. The TAMs represent up to 30% of the glioblastoma mass. The role of TAMs in tumor progression and in the mechanisms underlying tumor growth remain unclear. Using an in vitro model resembling the crosstalk between macrophages and glioblastoma cells, we show that glioblastoma-derived exosomes (GBex) reprogram M1 (mediate pro-inflammatory function) and M2 (mediate anti-inflammatory function) macrophages, converting M1 into TAMs and augmenting pro-tumor functions of M2 macrophages. In turn, these GBex-reprogrammed TAMs, produce exosomes decorated by immunosuppressive and tumor-growth promoting proteins. TAM-derived exosomes disseminate these proteins in the tumor microenvironment (TME) promoting tumor cell migration and proliferation. Mechanisms underlying the promotion of glioblastoma growth involved Arginase-1+ exosomes produced by the reprogrammed TAMs. A selective Arginase-1 inhibitor, nor-NOHA reversed growth-promoting effects of Arginase-1 carried by TAM-derived exosomes. The data suggest that GBex-reprogrammed Arginase-1+ TAMs emerge as a major source of exosomes promoting tumor growth and as a potential therapeutic target in glioblastoma.

scholarly journals PUMILIO Proteins in Colorectal Cancer: Tumor Growth Promoting Function and Potential as Therapeutic Targets

2021 ◽  
Author(s):  
Yuanyuan Gong ◽  
Zukai Liu ◽  
Yihang Yuan ◽  
Zhenzhen Yang ◽  
Jiawei Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Therapeutic Targets ◽  
Cancer Models ◽  
Cancer Tumor ◽  
Direct Target ◽  
Growth Promoting ◽  
Pumilio Proteins ◽  
Puf Family

Abstract PUMILIO (PUM) proteins belong to the highly conserved PUF family post-transcriptional regulators involved in diverse biological processes. However, their function in carcinogenesis remains under explored. Here, we found that the expression of Pum1 and Pum2 are increased in clinical colorectal cancer (CRC). Intestine-specific knockout of Pum1 and Pum2 significantly inhibited the progression of colitis associated cancer in the AOM/DSS model. Knockout or knockdown of Pum1 and/or Pum2 resulted in a significant decrease in the tumorigenicity. In addition, delayed G1/S transition was observed. We identified p21/Cdkn1a as direct target of PUM1, and abrogation of the PUM1 binding site in p21 resulted in decreased tumor cell growth as well as delayed G1/S transition. Furthermore, intravenous injection of nanoparticle-encapsulated anti-Pum1 and Pum2 siRNAs reduced colorectal tumor growth in murine orthotopic colon cancer models. These findings reveal a tumor growth promoting role of PUM proteins in CRC and its potential as therapeutic targets.

scholarly journals PTK787/ZK 222584 inhibits tumor growth promoting mesenchymal stem cells: Kinase activity profiling as powerful tool in functional studies

2009 ◽  
Vol 8 (13) ◽  
pp. 1239-1248 ◽  
Author(s):  
Berber Roorda ◽  
Arja ter Elst ◽  
Sander H. Diks ◽  
Tiny G. J. Meeuwsen-de Boer ◽  
Willem A. Kamps ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Kinase Activity ◽  
Functional Studies ◽  
Activity Profiling ◽  
Growth Promoting
Sign in / Sign up

Export Citation Format

Share Document