Erythroid potentiating activity of tissue inhibitor of metalloproteinases on the differentiation of erythropoietin-responsive mouse erythroleukemia cell line, ELM-I-1-3, is closely related to its cell growth potentiating activity.
The erythroid-potentiating activity (EPA) of the tissue inhibitor of metalloproteinase-1 (TIMP-1) was re-examined using ELM-I-1-3, a mouse erythroleukemia cell line, which responded well to erythropoietin. Depletion of pre-existing TIMP-1 from fetal calf serum in culture medium using monoclonal antibody suppressed erythropoietin-induced differentiation as measured by the induction of hemoglobin, commitment assay and globin mRNAs. The removal of TIMP-1 also suppressed the proliferation of ELM-I-1-3 as measured by cell number and de novo DNA synthesis. These changes were reversed by the addition of purified TIMP-1 to the culture medium. Anti-TIMP-1 antibody also blocked both hexamethylene bisacetamide (HMBA)-induced erythroid differentiation and the proliferation of both ELM-I-1-3 and Friend erythroleukemia cells. Considering previous reports analyzing the chemical induction of Friend mouse erythroleukemia cell differentiation, our results suggest that erythropoietin- or HMBA-induced erythroid differentiation might also be coupled with cell proliferation. Our 3H thymidine-uptake experiment shows that TIMP-1 removal was also effective in the inhibition of cell growth of various other cell lines in addition to erythroleukemia cell lines. These results suggest that EPA action of TIMP-1 on erythroid leukemia cell lines is closely related to its activity to promote the cell growth of various cell lines and cells including erythroleukemia cell lines.
Murate
T
T
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Yamashita
K
K
Ohashi
H
H
Kagami
Y
Y
Tsushita
K
K
Kinoshita
T
T
Hotta
T
T
Saito
H
H
Yoshida
S
S
Mori
K J
KJ
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D015672:Erythroid Precursor Cells / Q000473:pathology*; D004921:Erythropoietin / Q000494:pharmacology*; D005622:Friend murine leukemia virus; D015870:Gene Expression; D005914:Globins / Q000235:genetics; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D019714:Tissue Inhibitor of Metalloproteinases; D014407:Tumor Cells, Cultured
D000081:Acetamides; D000906:Antibodies; D004273:DNA, Neoplasm; D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D004921:Erythropoietin; D005914:Globins; C014026:hexamethylene bisacetamide