[Modulation of invasiveness and invasion/metastasis-associated gene expression of a mouse mammary adenocarcinoma by interferons].
OBJECTIVE
To investigate the effects of IFNs on the in vitro invasiveness and the expression of several genes related to invasion and metastatic behavior of MA-891 cells.


METHODS
The invasiveness was assessed by penetration through a matrigel-coated filter. Cell surface antigen and mRNA levels were analyzed by flow cytometry and Northern blot respectively.


RESULTS
IFN-gamma pretreatment increased the invasiveness of MA-891 (P < 0.01). Pretreatment with IFN-alpha decreased the invasiveness of cells, but it was not statistically significant. Cell surface ICAM-1 was not found on MA-891 cells even after treatment with IFN-alpha, but was strongly induced after IFN-gamma treatment. Another adhesion molecule CD44v mRNA, absent on MA-891 cells, could not be induced to express by either IFN. Both 72,000 and 92,000 type IV collagenase mRNAs were detectable in MA-891 cells. The 72 kD-type IV collagenase expression was up-regulated by IFN-gamma and IFN-alpha, but the levels of expression were significantly higher in cells treated with IFN-gamma than those treated with IFN-alpha. IFN-gamma and IFN-alpha treatment had little or no effect on expression of the 92,000 type IV collagenase. Treatment with IFN-gamma had no effects on antimetastasis nm23 gene expression whereas treatment with IFN-alpha resulted in marked up-regulation of its expression.


CONCLUSIONS
IFN-gamma and IFN-alpha differ in their effects on the expression of genes related to invasion and metastasis of MA-891 cells, thereby differentially modulating metastatic potential.
Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
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Luo
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Zhang
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Huang
D016475:3T3 Cells / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D017364:Collagenases / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D009701:Nucleoside-Diphosphate Kinase; D011994:Recombinant Proteins; D014157:Transcription Factors / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000378:metabolism
D007370:Interferon Type I; D054778:NM23 Nucleoside Diphosphate Kinases; D011994:Recombinant Proteins; D014157:Transcription Factors; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D017364:Collagenases; D020559:Monomeric GTP-Binding Proteins