Interleukin-6 increases expression and secretion of cathepsin B by breast tumor-associated monocytes.
In the tumor microenvironment, monocytes respond to paracrine stimuli from breast cancer cells by secreting molecules that participate in breast cancer growth, invasion, intravasation and metastasis. Here we examined the effects of media conditioned by MDA-MB-231 human breast carcinoma cells (231-CM) on expression and secretion of proteases and secretion of cytokines by U937 human monocytes. We found that 231-CM increased U937: 1) proliferation; 2) expression, activity and secretion of the cysteine protease cathepsin B (CTSB); 3) secretion of matrix metalloproteinases (MMP)-2 and -9; and 4) secretion of interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1). We further demonstrated by western blotting and enzymatic activity assays that the increases in CTSB secretion and activity induced by 231-CM could be reduced by neutralizing antibodies against IL-6. Our data suggest a role for IL-6 in increased monocyte expression and secretion of CTSB in response to soluble factors secreted by breast cancer cells.
Mohamed
Mona M
MM
Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt. monamos@link.net
Cavallo-Medved
Dora
D
Rudy
Deborah
D
Anbalagan
Arulselvi
A
Moin
Kamiar
K
Sloane
Bonnie F
BF
D001943:Breast Neoplasms / Q000201:enzymology* / Q000276:immunology; D002401:Cathepsin B / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology
D018970:Insulin-Like Growth Factor Binding Protein 1; D015850:Interleukin-6; D002401:Cathepsin B; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9