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 vrtro production of cytokines with chemotactic, pro‐ inflammatory 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‐) la 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)‐I. MCP‐I 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. © 1995 Wiley‐Liss, Inc.

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