An in vivo model to compare human leukocyte infiltration in carcinoma xenografts producing different chemokines.
In this study we tested whether the pattern of cytokines expressed by human carcinomas could account for a different in vivo recruitment of leukocyte subpopulations as a part of the anti-tumor immune response. Two carcinoma cell lines, SK-OV-3 ovary carcinoma and CALU-3 lung carcinoma, were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence and ELISA for the expression and in vitro production of cytokines with chemotactic, proinflammatory and growth-stimulating activity. Although both cell lines displayed a constitutive expression of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage-CSF (GM-CSF), M-CSF, interleukin (IL-) 1 alpha and IL-8, only CALU-3 cell line expressed IL-10, RANTES (Regulated upon Activation, Normal T Expressed and Secreted) and monocyte-activating protein (MCP)-1. MCP-1 and IL-8 were detected by immunohistochemistry on sections from tumors xenografted in nude mice. To analyze whether the tumor-released cytokines modulate leukocytes in tumor infiltration, we studied the distribution of human peripheral blood leukocytes injected in the proximity of SK-OV-3 and of CALU-3 tumor xenografts. While SK-OV-3 was unable to recruit human leukocytes and appeared to be barely infiltrated by murine CD45+ cells, CALU-3 appeared to be rapidly and heavily infiltrated by human leukocytes which induced tumor necrosis within 18-24 hr.
Melani
C
C
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Pupa
S M
SM
Stoppacciaro
A
A
Ménard
S
S
Colnaghi
M I
MI
Parmiani
G
G
Colombo
M P
MP
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology*; D012334:RNA, Neoplasm / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016207:Cytokines; D017931:DNA Primers; D012334:RNA, Neoplasm