Origin of histiocyte-like cells and multinucleated giant cells in malignant fibrous histiocytoma: neoplastic or reactive?
The origin of histiocyte-like cells in malignant fibrous histiocytoma (MFH) remains controversial. To determine whether histiocyte-like cells and multinucleated giant cells show reactive or neoplastic proliferation, we transplanted human storiform-pleomorphic MFH to nude mice and investigated the origin of histiocyte-like cells using the DNA in situ hybridization (ISH) system. In addition, we analyzed the mRNA expression of mouse c-fms and human colony stimulating factor-1 (CSF-1); immunohistochemical expression of markers detectable in cells of monocyte/macrophage lineage. The DNA ISH revealed neoplastic proliferation of fibroblastic cells and bizarre multinucleated giant cells of human origin. Monocyte/macrophage lineage cells were seen in parental tumors, whereas they did not participate in neoplastic proliferation in transplanted tumors. The parental tumors expressed human CSF-1 mRNA and the histiocyte-like cells in transplanted tumors expressed 'mouse' c-fms mRNA. These results suggest that MFH induce infiltration of monocyte/macrophage and CSF-1 is one of the mediators involved in this phenomenon, because the human CSF-1 can act as a ligand to the mouse c-fms. Histiocyte-like cells in MFH should be considered as a reactive monocyte/macrophage lineage rather than as an element of neoplasm.
Hatano
H
H
Department of Orthopedic Surgery, Niigata University School of Medicine, Niigata City, Japan. hatan@med.niigata-u.ac.jp
Tokunaga
K
K
Ogose
A
A
Imaizumi
S
S
Hayami
T
T
Yamagiwa
H
H
Hotta
T
T
Endo
N
N
Takahashi
H E
HE
Naito
M
M
D000368:Aged; D020087:Alu Elements; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015726:Giant Cells / Q000737:chemistry / Q000473:pathology*; D006684:HLA-DR Antigens / Q000032:analysis; D006644:Histiocytes / Q000737:chemistry / Q000473:pathology*; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D008264:Macrophages / Q000737:chemistry / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D018626:Retroelements; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015342:DNA Probes; D004273:DNA, Neoplasm; D006684:HLA-DR Antigens; D016173:Macrophage Colony-Stimulating Factor; D015347:RNA Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016186:Receptor, Macrophage Colony-Stimulating Factor; D018626:Retroelements; C067980:CD68 antigen, human; D000097382:CD68 Molecule