Abstract
The aim of this study was to discover whether MCP-1/CCL2, a CC chemokine able to attract macrophages, is expressed in human pancreatic cancer and how it modulates cancer progression. All primary tumors were tested, and 6 of 14 pancreatic cancer cell lines were constitutively secreted CCL2. Analysis of the regulation demonstrated that the expression of CCL2 was significantly elevated and in a synergistic manner by IFN-γ, tumor necrosis factor α, and interleukin 1β. By immunohistochemistry and in situ hybridization, CCL2 production was confirmed in neoplastic ducts from surgical specimens. Serum levels of CCL2 in pancreatic cancer patients were significantly higher than in normal healthy subjects (P <0.0001). Patients with high circulating levels of CCL2 had significantly higher survival rate than low CCL2 producers. Serum CCL2 levels positively correlated with tumor macrophage infiltration and inversely correlated with tumor proliferative activity (Ki67 expression). A direct effect of CCL2 on tumor cells is to be excluded, either because primary tumors as well as cell lines have no detectable CCL2 receptor (CCR2) and because addition of CCL2 on tumor cells in vitro did not modify cell cycle progression or apoptosis. In vitro, a model of tumor microenvironment showed a direct antiproliferative and proapoptotic activity of monocytes toward pancreatic cancer cell, which is mediated at least in part by interleukin 1β. Moreover, other proinflammatory cytokines such as tumor necrosis factor α and IFN-γ appeared able to induce apoptosis and to reduce the proliferative rate of pancreatic cancer. On the whole, the results presented in our investigation suggest that CCL2 could be a relevant negative regulator of pancreatic cancer progression.
| Original language | English |
|---|---|
| Pages (from-to) | 7451-7461 |
| Number of pages | 11 |
| Journal | Cancer Research |
| Volume | 63 |
| Issue number | 21 |
| Publication status | Published - Nov 1 2003 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
The CC Chemokine MCP-1/CCL2 in Pancreatic Cancer Progression : Regulation of Expression and Potential Mechanisms of Antimalignant Activity. / Monti, Paolo; Leone, Biagio Eugenio; Marchesi, Federica; Balzano, Gianpaolo; Zerbi, Alessandro; Scaltrini, Francesca; Pasquali, Claudio; Calori, Giliola; Pessi, Francesca; Sperti, Cosimo; Di Carlo, Valerio; Allavena, Paola; Piemonti, Lorenzo.
In: Cancer Research, Vol. 63, No. 21, 01.11.2003, p. 7451-7461.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The CC Chemokine MCP-1/CCL2 in Pancreatic Cancer Progression
T2 - Regulation of Expression and Potential Mechanisms of Antimalignant Activity
AU - Monti, Paolo
AU - Leone, Biagio Eugenio
AU - Marchesi, Federica
AU - Balzano, Gianpaolo
AU - Zerbi, Alessandro
AU - Scaltrini, Francesca
AU - Pasquali, Claudio
AU - Calori, Giliola
AU - Pessi, Francesca
AU - Sperti, Cosimo
AU - Di Carlo, Valerio
AU - Allavena, Paola
AU - Piemonti, Lorenzo
PY - 2003/11/1
Y1 - 2003/11/1
N2 - The aim of this study was to discover whether MCP-1/CCL2, a CC chemokine able to attract macrophages, is expressed in human pancreatic cancer and how it modulates cancer progression. All primary tumors were tested, and 6 of 14 pancreatic cancer cell lines were constitutively secreted CCL2. Analysis of the regulation demonstrated that the expression of CCL2 was significantly elevated and in a synergistic manner by IFN-γ, tumor necrosis factor α, and interleukin 1β. By immunohistochemistry and in situ hybridization, CCL2 production was confirmed in neoplastic ducts from surgical specimens. Serum levels of CCL2 in pancreatic cancer patients were significantly higher than in normal healthy subjects (P <0.0001). Patients with high circulating levels of CCL2 had significantly higher survival rate than low CCL2 producers. Serum CCL2 levels positively correlated with tumor macrophage infiltration and inversely correlated with tumor proliferative activity (Ki67 expression). A direct effect of CCL2 on tumor cells is to be excluded, either because primary tumors as well as cell lines have no detectable CCL2 receptor (CCR2) and because addition of CCL2 on tumor cells in vitro did not modify cell cycle progression or apoptosis. In vitro, a model of tumor microenvironment showed a direct antiproliferative and proapoptotic activity of monocytes toward pancreatic cancer cell, which is mediated at least in part by interleukin 1β. Moreover, other proinflammatory cytokines such as tumor necrosis factor α and IFN-γ appeared able to induce apoptosis and to reduce the proliferative rate of pancreatic cancer. On the whole, the results presented in our investigation suggest that CCL2 could be a relevant negative regulator of pancreatic cancer progression.
AB - The aim of this study was to discover whether MCP-1/CCL2, a CC chemokine able to attract macrophages, is expressed in human pancreatic cancer and how it modulates cancer progression. All primary tumors were tested, and 6 of 14 pancreatic cancer cell lines were constitutively secreted CCL2. Analysis of the regulation demonstrated that the expression of CCL2 was significantly elevated and in a synergistic manner by IFN-γ, tumor necrosis factor α, and interleukin 1β. By immunohistochemistry and in situ hybridization, CCL2 production was confirmed in neoplastic ducts from surgical specimens. Serum levels of CCL2 in pancreatic cancer patients were significantly higher than in normal healthy subjects (P <0.0001). Patients with high circulating levels of CCL2 had significantly higher survival rate than low CCL2 producers. Serum CCL2 levels positively correlated with tumor macrophage infiltration and inversely correlated with tumor proliferative activity (Ki67 expression). A direct effect of CCL2 on tumor cells is to be excluded, either because primary tumors as well as cell lines have no detectable CCL2 receptor (CCR2) and because addition of CCL2 on tumor cells in vitro did not modify cell cycle progression or apoptosis. In vitro, a model of tumor microenvironment showed a direct antiproliferative and proapoptotic activity of monocytes toward pancreatic cancer cell, which is mediated at least in part by interleukin 1β. Moreover, other proinflammatory cytokines such as tumor necrosis factor α and IFN-γ appeared able to induce apoptosis and to reduce the proliferative rate of pancreatic cancer. On the whole, the results presented in our investigation suggest that CCL2 could be a relevant negative regulator of pancreatic cancer progression.
UR - http://www.scopus.com/inward/record.url?scp=10744234018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744234018&partnerID=8YFLogxK
M3 - Article
C2 - 14612545
AN - SCOPUS:10744234018
VL - 63
SP - 7451
EP - 7461
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 21
ER -