Potential osteogenic differentiation of cisplatin-resistant rat malignant fibrous histiocytoma-derived cell lines

Exp Toxicol Pathol. 2007 Apr;58(5):299-309. doi: 10.1016/j.etp.2006.11.008. Epub 2007 Jan 30.


Histological modulations in tumor cells treated with anti-cancer drugs have been reported. The histogenesis of malignant fibrous histiocytoma (MFH) remains elusive. To investigate cellular characteristics and alterations, therefore, we derived cisplatin-resistant MFH cell lines (MT-PR and MT-10R) from MT-P and MT-10, respectively, and compared them with MT-10, a non-cisplatin-resistant MFH line (MT-10 was isolated as a clone cell line from MT-P, and MT-P was originally established from a rat spontaneous MFH). Immunohistochemically, MT-10 reacted to vimentin, alpha-smooth muscle actin (a marker of myofibroblasts), ED1/ED2 (rat macrophage/histiocyte-specific antibodies), and A3 (rat MFH-specific antibody) in varying degrees, indicating that MFH cells have features of both fibroblasts and histiocytes. However, MT-10R and MT-PR reduced ED1-positive cell numbers. MT-10 developed tumors of a storiform pattern, while MT-10R and MT-PR tumors comprise round or polygonal cells arranged in a compact sheet. Additionally, MT-PR tumors included ossifying areas. MT-10R and MT-PR, and their tumors showed a reaction to alkaline phosphatase (ALP), a marker of osteoblasts. RT-PCR revealed that mRNAs of bone morphogenetic protein (BMP)-2, BMP-6 and osteopontin were significantly increased in MT-10R and MT-PR tumors. Neoplastic cells in these tumors were immunoreactive to BMP-2 and BMP-6, while MT-10 tumors were not. Cisplatin-resistant MFH cells had potential to differentiate into osteogenic tissues by producing osteogenic factors, suggesting that MFH histology may be altered under anti-cancer drug treatments. Recently, cancer differentiation-based therapy, that could be induced by anti-cancer drugs, has been implied. MT-10R and MT-PR become useful experimental systems for studies on cellular differentiation provoked by anti-cancer drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 1
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Proteins / biosynthesis*
  • Cell Differentiation / drug effects*
  • Cisplatin / pharmacology*
  • Clone Cells
  • Drug Resistance, Neoplasm / drug effects*
  • Enzyme-Linked Immunosorbent Assay
  • Histiocytoma, Malignant Fibrous / metabolism
  • Histiocytoma, Malignant Fibrous / pathology*
  • Immunohistochemistry
  • Metalloendopeptidases / biosynthesis
  • Neoplasm Transplantation
  • Osteoblasts / metabolism
  • Osteoblasts / pathology*
  • Osteopontin / biosynthesis
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Inbred F344
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • Bmp6 protein, rat
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Proteins
  • RNA, Messenger
  • Osteopontin
  • Metalloendopeptidases
  • Bmp1 protein, rat
  • Bone Morphogenetic Protein 1
  • Cisplatin