Unique human CD133+ leukemia cell line and its modulation towards a mesenchymal phenotype by FGF2 and TGFbeta1.
Immunological features of GM-490 cells, a new blood cell line from a patient with acute lymphoblastic leukemia, included lack of CD34, CD38, CD45, CD14, HLA-DR, and lymphoid and myeloid markers and expression of CD29, CD36, CD44, CD54, CD71, CD105, and CD133. Molecular analysis indicated CD45 gene expression was absent but CD34 mRNA was present. GM-490 cells constitutively produced fibronectin (FN), type III and traces of type I collagen, collagenases, glycosaminoglycans (GAG) and biglycan and betaglycan proteoglycans (PG) as well as FGF2 and TGFbeta1. When FGF2 and/or TGFbeta1 were added to cells in vitro, they stimulated cell proliferation and differently modulated matrix production and growth factor receptor expression. Reverse transcription-polymerase chain reaction (RT-PCR) detection of transcripts encoding for osteocalcin and RUNX2 suggests GM-490 cells differentiate towards the osteoblast pathway. GM-490 cells expressed the low affinity nerve growth factor receptor (p75LNGFR), a somatic stem cell marker that is not detected in hematopoietic cells, leading to the hypothesis that GM-490 has mesenchymal stem cell properties. The reciprocal modulating effects of FGF2 and TGFbeta1 on each other's receptors make the GM-490 cell line a new model for investigating the relationship between these growth factors and their receptors in autocrine loops which are believed to sustain the malignant clone in hematological diseases.
Bodo
Maria
M
Histology Section, Faculty of Medicine, University of Perugia, Perugia, Italy. bodo@unipg.it
Baroni
Tiziano
T
Bellucci
Catia
C
Lilli
Cinzia
C
De Ioanni
Maria
M
Bonifacio
Elisabetta
E
Moretti
Lorenzo
L
Becchetti
Ennio
E
Bellocchio
Silvia
S
Delfini
Costante
C
Lumare
Eleonora
E
Tabilio
Antonio
A
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D017364:Collagenases / Q000378:metabolism; D003114:Colony-Forming Units Assay; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D005353:Fibronectins / Q000096:biosynthesis; D006023:Glycoproteins / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D015675:Osteocalcin / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D012333:RNA, Messenger / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*
D000071916:AC133 Antigen; D015703:Antigens, CD; D050659:Core Binding Factor Alpha 1 Subunit; D005353:Fibronectins; D006023:Glycoproteins; D006025:Glycosaminoglycans; C000606023:PROM1 protein, human; D010455:Peptides; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D015675:Osteocalcin; D003094:Collagen; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017364:Collagenases