Human astrocytomas and glioblastomas express monocyte chemoattractant protein‐1 (MCP‐1) <i>in vivo</i> and <i>in vitro</i>

Desbaillets, Isabelle; Tada, Mitsuhiro; Tribolet, Nicolas de; Diserens, A.-C.; Hamou, Marie‐France; Meir, Erwin G. Van

doi:10.1002/ijc.2910580216

Cited by 136 publications

(89 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MCP-1 is a CC chemokine that induces the migration of monocytes, memory T cells, and NK cells. MCP-1 is expressed by human astrogliomas in vivo and in vitro (73,74). Infiltrating macrophages are a common feature of human gliomas, and the extent of macrophage infiltration correlates with the level of MCP-1 expression (74).…”

Section: Discussionmentioning

confidence: 99%

CXC Chemokine Receptor 4 Expression and Function in Human Astroglioma Cells

Drabik

Kutsch

et al. 2001

The Journal of Immunology

104

View full text Add to dashboard Cite

Chemokines constitute a superfamily of proteins that function as chemoattractants and activators of leukocytes. Astrocytes, the major glial cell type in the CNS, are a source of chemokines within the diseased brain. Specifically, we have shown that primary human astrocytes and human astroglioma cell lines produce the CXC chemokines IFN-γ-inducible protein-10 and IL-8 and the CC chemokines monocyte chemoattractant protein-1 and RANTES in response to stimuli such as TNF-α, IL-1β, and IFN-γ. In this study, we investigated chemokine receptor expression and function on human astroglioma cells. Enhancement of CXC chemokine receptor 4 (CXCR4) mRNA expression was observed upon treatment with the cytokines TNF-α and IL-1β. The peak of CXCR4 expression in response to TNF-α and IL-1β was 8 and 4 h, respectively. CXCR4 protein expression was also enhanced upon treatment with TNF-α and IL-1β (2- to 3-fold). To study the functional relevance of CXCR4 expression, stable astroglioma transfectants expressing high levels of CXCR4 were generated. Stimulation of cells with the ligand for CXCR4, stromal cell-derived factor-1α (SDF-1α), resulted in an elevation in intracellular Ca2+ concentration and activation of the mitogen-activated protein kinase cascade, specifically, extracellular signal-regulated kinase 2 (ERK2) mitogen-activated protein kinase. Of most interest, SDF-1α treatment induced expression of the chemokines monocyte chemoattractant protein-1, IL-8, and IFN-γ-inducible protein-10. SDF-1α-induced chemokine expression was abrogated upon inclusion of U0126, a pharmacological inhibitor of ERK1/2, indicating that the ERK signaling cascade is involved in this response. Collectively, these data suggest that CXCR4-mediated signaling pathways in astroglioma cells may be another mechanism for these cells to express chemokines involved in angiogenesis and inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

CXC Chemokine Receptor 4 Expression and Function in Human Astroglioma Cells

Drabik

Kutsch

et al. 2001

The Journal of Immunology

104

View full text Add to dashboard Cite

show abstract

“…The role of MCP-1 in tumor development and progression is less clear. Expression has been reported for melanoma (13), glioma (14,15), sarcoma (16,17), leukemia (18), hemangioma (19), and carcinomas of breast (20), cervix (21,22), and ovary (23). The malignant cells express MCP-1, apparently due to the constitutive production of activating growth factors and cytokines such as IL-1 (24), TGF-␤ (25), and platelet-derived growth factor (26,27).…”

Section: S Olid Human Tumors Are Often Infiltrated By Host Immunementioning

confidence: 99%

Low-Level Monocyte Chemoattractant Protein-1 Stimulation of Monocytes Leads to Tumor Formation in Nontumorigenic Melanoma Cells

Nesbit

Schaider

Miller

et al. 2001

The Journal of Immunology

206

162

View full text Add to dashboard Cite

Tumors commonly produce chemokines for recruitment of host cells, but the biological significance of tumor-infiltrating inflammatory cells, such as monocytes/macrophages, for disease outcome is not clear. Here, we show that all of 30 melanoma cell lines secreted monocyte chemoattractant protein-1 (MCP-1), whereas normal melanocytes did not. When low MCP-1-producing melanoma cells from a biologically early, nontumorigenic stage were transduced to overexpress the MCP-1 gene, tumor formation depended on the level of chemokine secretion and monocyte infiltration; low-level MCP-1 secretion with modest monocyte infiltration resulted in tumor formation, whereas high secretion was associated with massive monocyte/macrophage infiltration into the tumor mass, leading to its destruction within a few days after injection into mice. Tumor growth stimulated by monocytes/macrophages was due to increased angiogenesis. Vessel formation in vitro was inhibited with mAbs against TNF-α, which, when secreted by cocultures of melanoma cells with human monocytes, induced endothelial cells under collagen gels to form branching, tubular structures. These studies demonstrate that the biological effects of tumor-derived MCP-1 are biphasic, depending on the level of secretion. This correlates with the degree of monocytic cell infiltration, which results in increased tumor vascularization and TNF-α production.

show abstract

“…Northern blots were prepared with 10 mg of RNA/sample as previously described (Desbaillets et al, 1994). The probes and washing conditions used were identical to our previous report .…”

Section: Northern Blot Analysismentioning

confidence: 99%