Abstract
Injection of interleukin-4 (IL4) gene-transduced tumour cells into syngeneic immunocompetent mice resulted in turnout rejection in which a key role for eosinophils was suggested. To evaluate whether IL5 inhibits turnout growth by selectively inducing eosinophil recruitment and activation, a poorly differentiated mammary adenocarcinoma cell line (TSA) was transfected with the IL5 gene and the cells secreting IL5 (TSA-IL5) were injected subcutaneously (s.c,) in syngeneic mice. The oncogenicity of TSA-IL5 was compared with that exhibited by TSA cells transfected with the IL4 gene (TSA- IL4) and with the neomycin resistance gene only (TSA-neo). At progressive times after subcutaneous challenge, tumour growth areas were studied histologically, ultrastructurally, and immunohistochemically to identify the reactive cells, visualize tumour vessels, and detect the cytokines and chemokines involved in the anti-tumour reaction. Both the morphological and the functional data showed that TSA-IL5, despite the large eosinophil infiltrate, grew progressively like TSA-neo, suggesting that eosinophils per se do not play a crucial role in TSA tumour rejection. Furthermore, our data indicate that the rejection of TSA-IL4 depends on the IL4-induced expression of VCAM-1 and MCP-1 by endothelial cells. MCP-1 together with VCAM-1 results in recruitment and activation of basophils, mast cells, and macrophages, and hence a pro-inflammatory cytokine cascade that initially favours the influx and activation of neutrophils and finally tumour rejection. In this context, the rejection of TSA-IL4 seems to involve a variety of reactive cells and rests on a continuous cross-talk between basophils, mast cells, macrophages, CD8-positive lymphocytes, and granulocyte subsets, mostly neutrophils.
| Original language | English |
|---|---|
| Pages (from-to) | 390-397 |
| Number of pages | 8 |
| Journal | Journal of Pathology |
| Volume | 186 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1998 |
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Keywords
- Adhesion molecules
- Chemokines
- Cytokines
- Endothelial cells
- Gene therapy
- IL4
- IL5
- Mouse mammary adenocarcinoma
- Neutrophils
- Tumour growth
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Interaction between endothelial cells and the secreted cytokine drives the fate of an IL4- or an IL5-transduced tumour. / Di Carlo, Emma; Modesti, Andrea; Coletti, Anna; Colombo, Mario P.; Giovarelli, Mirella; Forni, Guido; Diodoro, Maria G.; Musiani, Piero.
In: Journal of Pathology, Vol. 186, No. 4, 1998, p. 390-397.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interaction between endothelial cells and the secreted cytokine drives the fate of an IL4- or an IL5-transduced tumour
AU - Di Carlo, Emma
AU - Modesti, Andrea
AU - Coletti, Anna
AU - Colombo, Mario P.
AU - Giovarelli, Mirella
AU - Forni, Guido
AU - Diodoro, Maria G.
AU - Musiani, Piero
PY - 1998
Y1 - 1998
N2 - Injection of interleukin-4 (IL4) gene-transduced tumour cells into syngeneic immunocompetent mice resulted in turnout rejection in which a key role for eosinophils was suggested. To evaluate whether IL5 inhibits turnout growth by selectively inducing eosinophil recruitment and activation, a poorly differentiated mammary adenocarcinoma cell line (TSA) was transfected with the IL5 gene and the cells secreting IL5 (TSA-IL5) were injected subcutaneously (s.c,) in syngeneic mice. The oncogenicity of TSA-IL5 was compared with that exhibited by TSA cells transfected with the IL4 gene (TSA- IL4) and with the neomycin resistance gene only (TSA-neo). At progressive times after subcutaneous challenge, tumour growth areas were studied histologically, ultrastructurally, and immunohistochemically to identify the reactive cells, visualize tumour vessels, and detect the cytokines and chemokines involved in the anti-tumour reaction. Both the morphological and the functional data showed that TSA-IL5, despite the large eosinophil infiltrate, grew progressively like TSA-neo, suggesting that eosinophils per se do not play a crucial role in TSA tumour rejection. Furthermore, our data indicate that the rejection of TSA-IL4 depends on the IL4-induced expression of VCAM-1 and MCP-1 by endothelial cells. MCP-1 together with VCAM-1 results in recruitment and activation of basophils, mast cells, and macrophages, and hence a pro-inflammatory cytokine cascade that initially favours the influx and activation of neutrophils and finally tumour rejection. In this context, the rejection of TSA-IL4 seems to involve a variety of reactive cells and rests on a continuous cross-talk between basophils, mast cells, macrophages, CD8-positive lymphocytes, and granulocyte subsets, mostly neutrophils.
AB - Injection of interleukin-4 (IL4) gene-transduced tumour cells into syngeneic immunocompetent mice resulted in turnout rejection in which a key role for eosinophils was suggested. To evaluate whether IL5 inhibits turnout growth by selectively inducing eosinophil recruitment and activation, a poorly differentiated mammary adenocarcinoma cell line (TSA) was transfected with the IL5 gene and the cells secreting IL5 (TSA-IL5) were injected subcutaneously (s.c,) in syngeneic mice. The oncogenicity of TSA-IL5 was compared with that exhibited by TSA cells transfected with the IL4 gene (TSA- IL4) and with the neomycin resistance gene only (TSA-neo). At progressive times after subcutaneous challenge, tumour growth areas were studied histologically, ultrastructurally, and immunohistochemically to identify the reactive cells, visualize tumour vessels, and detect the cytokines and chemokines involved in the anti-tumour reaction. Both the morphological and the functional data showed that TSA-IL5, despite the large eosinophil infiltrate, grew progressively like TSA-neo, suggesting that eosinophils per se do not play a crucial role in TSA tumour rejection. Furthermore, our data indicate that the rejection of TSA-IL4 depends on the IL4-induced expression of VCAM-1 and MCP-1 by endothelial cells. MCP-1 together with VCAM-1 results in recruitment and activation of basophils, mast cells, and macrophages, and hence a pro-inflammatory cytokine cascade that initially favours the influx and activation of neutrophils and finally tumour rejection. In this context, the rejection of TSA-IL4 seems to involve a variety of reactive cells and rests on a continuous cross-talk between basophils, mast cells, macrophages, CD8-positive lymphocytes, and granulocyte subsets, mostly neutrophils.
KW - Adhesion molecules
KW - Chemokines
KW - Cytokines
KW - Endothelial cells
KW - Gene therapy
KW - IL4
KW - IL5
KW - Mouse mammary adenocarcinoma
KW - Neutrophils
KW - Tumour growth
UR - http://www.scopus.com/inward/record.url?scp=0032412860&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032412860&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1096-9896(199812)186:4<390::AID-PATH194>3.0.CO;2-Z
DO - 10.1002/(SICI)1096-9896(199812)186:4<390::AID-PATH194>3.0.CO;2-Z
M3 - Article
C2 - 10209488
AN - SCOPUS:0032412860
VL - 186
SP - 390
EP - 397
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 4
ER -