AUGMENTED EXPRESSION OF CYTOKINES IN MOUSE EPIDERMAL TUMOR-CELLS AND ITS POSSIBLE INVOLVEMENT IN THE INDUCTION OF HEMATOPOIETIC ALTERATIONS

Citation
C. Bauluz et al., AUGMENTED EXPRESSION OF CYTOKINES IN MOUSE EPIDERMAL TUMOR-CELLS AND ITS POSSIBLE INVOLVEMENT IN THE INDUCTION OF HEMATOPOIETIC ALTERATIONS, Molecular carcinogenesis, 11(3), 1994, pp. 155-163
Citations number
59
Categorie Soggetti
Oncology
Journal title
ISSN journal
08991987
Volume
11
Issue
3
Year of publication
1994
Pages
155 - 163
Database
ISI
SICI code
0899-1987(1994)11:3<155:AEOCIM>2.0.ZU;2-M
Abstract
Mice with skin tumors induced either by 7,12-dimethylbenz[a]anthracene complete carcinogenesis or subcutaneous injection of a carcinogenic k eratinocyte cell line showed moderate to severe splenomegaly as a resu lt of an increase in splenic granulocyte-macrophage and erythroid (ery throid burst-forming unit) progenitors. To test whether the observed a lterations involve the release of soluble factors by the epidermal com ponent of skin tumors, we used an in vitro approach. A series of mouse keratinocyte cell lines resembling progressive stages of skin carcino genesis and carrying either normal or activated Ha-ras genes were assa yed for their ability to produce the factors required for colony growt h of hematopoietic-committed progenitors. Only the conditioned media o f keratinocytes harboring activated Ha-ras genes were able to support the growth of granulocyte-macrophage colony-forming units. In addition , preincubation of normal bone-marrow cells with conditioned media fro m the transformed epidermal cell lines stimulated in vitro amplificati on of the hematopoietic granulocyte-macrophage progenitor compartment. To identify the possible factors responsible for the activities detec ted in the keratinocyte-conditioned media, we performed northern blot analysis using the cytokine probes granulocyte colony-stimulating fact or, macrophage colony-stimulating factor, granulocyte-macrophage colon y-stimulating factor, stem cell factor, interleukin-1 alpha, interleuk in-3, and tumor necrosis factor-alpha. The cell lines expressed differ ent cytokine mRNA combinations that positively correlated with the col ony-stimulating activity detected in the corresponding conditioned med ium. These results suggest that transformed epidermal tumor cells in v ivo may alter normal hematopoiesis as a consequence of the production of cytokines that act in autocrine or paracrine loops probably related to tumor growth. (C) 1994 Wiley-Liss, Inc.