Expression of G-CSF and GM-CSF in Human Meningiomas Correlates with Increased Tumor Proliferation and Vascularization

Braun, Bernhard; Lange, Manfred; Oeckler, R.; Mueller, Margareta M.

doi:10.1023/b:neon.0000027751.87894.f0

Cited by 35 publications

(25 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…G-CSF is ectopically expressed in several human tumors such as leukemia [172], bladder [173], pancreatic [174], cervical [175], ovarian [176], head and neck [177], colorectal [178] and breast carcinoma [179]. Similarly, some human cancers show elevated GM-CSF expression levels [31,180,181]. It is therefore not surprising that elevated numbers of circulating neutrophils are seen in a wide variety of human malignancies.…”

Section: Regulation Of Neutrophil Mobilization Recruitment and Activmentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

336

261

View full text Add to dashboard Cite

Neutrophils are myeloid cells that constitute 50-70 % of all white blood cells in the human circulation. Traditionally, neutrophils are viewed as the first line of defense against infections and as a major component of the inflammatory process. In addition, accumulating evidence suggest that neutrophils may also play a key role in multiple aspects of cancer biology. The possible involvement of neutrophils in cancer prevention and promotion was already suggested more than half a century ago, however, despite being the major component of the immune system, their contribution has often been overshadowed by other immune components such as lymphocytes and macrophages. Neutrophils seem to have conflicting functions in cancer and can be classified into anti-tumor (N1) and pro-tumor (N2) sub-populations. The aim of this review is to discuss the varying nature of neutrophil function in the cancer microenvironment with a specific emphasis on the mechanisms that regulate neutrophil mobilization, recruitment and activation.

show abstract

Section: Regulation Of Neutrophil Mobilization Recruitment and Activmentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

336

261

View full text Add to dashboard Cite

show abstract

“…Part of the specimen was histopathologically classified, according to WHO classification, and the proliferation index (PI) was determined as previously described 14 by 2 independent neuropathologists (Table I). Normal human meninges were obtained during autopsies from 3 patients with no evidence of neurological disease.…”

Section: Patientsmentioning

confidence: 99%

Toll‐like receptor‐4 is expressed in meningiomas and mediates the antiproliferative action of paclitaxel

Tichomirowa

Theodoropoulou

Daly

et al. 2008

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Meningiomas are the second most common type of brain and CNS tumors by histology. Surgery and radiotherapy are main treatment options, but meningiomas may be impossible to adequately resect or may regrow after surgery. In spite of many experimental attempts, there is no generally accepted chemotherapeutic approach. We have studied in a series of meningiomas the expression of the Toll-like receptor 4 (TLR4), which apart from its major role as a key factor of the innate immune system, is believed to play a role in tumorigenesis. All meningiomas studied expressed TLR4 mRNA and protein at variable degree. Paclitaxel, a ligand of TLR4, exhibited a dose-and time-dependent growth suppression in both monolayer and spheroid meningioma cell cultures. The knockdown of TLR4 with siRNA in meningioma cell cultures abrogated the inhibitory effect of paclitaxel. The suppressive action of paclitaxel on meningioma cell growth was enhanced in the presence of fluvastatin or the mitogen-actvated protein kinase (ERK1/2) inhibitor PD98059. At least part of the growth suppressive effect was mediated by the induction of apoptosis in meningioma cells by paclitaxel alone or in combination with fluvastatin. In conclusion, our in vitro results suggest that paclitaxel alone or in combination with other inhibitors of cell growth (statins, MAPK inhibitors) could provide a potential tool for the treatment of TLR4 expressing meningiomas.

show abstract

“…Furthermore, no reproducible influence on tumor growth rate has been reported (21,22). GM-CSF has also been reported to be secreted by some primary tumors (23)(24)(25)(26)(27) but, to the best of our knowledge, there are no reports to date showing the expression of GM-CSF by primary colon tumor tissues nor its possible effects on the proliferation of this tumor type. Furthermore, the molecular mechanisms involved in the ectopic expression of GM-CSF by tumor cells are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Immune-Dependent and Independent Antitumor Activity of GM-CSF Aberrantly Expressed by Mouse and Human Colorectal Tumors

et al. 2013

View full text Add to dashboard Cite

Granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF2) is a cytokine produced in the hematologic compartment that may enhance antitumor immune responses, mainly by activation of dendritic cells. Here, we show that more than one-third of human colorectal tumors exhibit aberrant DNA demethylation of the GM-CSF promoter and overexpress the cytokine. Mouse engraftment experiments with autologous and homologous colon tumors engineered to repress the ectopic secretion of GM-CSF revealed the tumor-secreted GM-CSF to have an immune-associated antitumor effect. Unexpectedly, an immune-independent antitumor effect was observed that depended on the ectopic expression of GM-CSF receptor subunits by tumors. Cancer cells expressing GM-CSF and its receptor did not develop into tumors when autografted into immunocompetent mice. Similarly, 100% of the patients with human colon tumors that overexpressed GM-CSF and its receptor subunits survived at least 5 years after diagnosis. These data suggest that expression of GM-CSF and its receptor subunits by colon tumors may be a useful marker for prognosis as well as for patient stratification in cancer immunotherapy.

show abstract

Expression of G-CSF and GM-CSF in Human Meningiomas Correlates with Increased Tumor Proliferation and Vascularization

Cited by 35 publications

References 39 publications

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Toll‐like receptor‐4 is expressed in meningiomas and mediates the antiproliferative action of paclitaxel

Immune-Dependent and Independent Antitumor Activity of GM-CSF Aberrantly Expressed by Mouse and Human Colorectal Tumors

Contact Info

Product

Resources

About