Novel models of myxoid liposarcoma xenografts mimicking the biological and pharmacologic features of human tumors.

Abstract

PURPOSE:

Myxoid liposarcoma is a common subtype of liposarcoma. It is associated in more than 90% of cases with the chromosomal translocation t(12;16)(q13;p11) leading to the fusion FUS-CHOP gene that is responsible for the oncogenic transformation of preadipocytes. Recently the marine natural product trabectedin has shown highly selective activity for myxoid liposarcoma, even in the most aggressive round-cell subtype.

EXPERIMENTAL DESIGN:

Fragments of 17 sarcomas were transplanted s.c. in female athymic NCr-nu/nu mice. Xenografts were established and characterized by morphology, fluorescence in situ hybridization analysis for the translocation and reverse transcriptase-PCR analysis for fusion transcripts. Trabectedin was injected i.v.

RESULTS:

Seven of 17 tumors grew as continuous xenografts, five of them being myxoid liposarcoma of the round-cell subtype. The chromosomal rearrangement and fusion transcripts in different passages were the same as in the human tumors from which they were derived. The responsiveness to trabectedin in type II myxoid liposarcoma xenografts was as high as in patients. The pathologic response was associated with the presence of the FUS-CHOP fusion gene, indicating that the drug does not totally eradicate the disease. Type III myxoid liposarcoma xenografts seemed much less sensitive to trabectedin, confirming previous clinical observations.

CONCLUSIONS:

This study reports for the first time the characterization of human myxoid liposarcoma xenografts that adequately mimic the biological and pharmacologic features of the human tumor. These models offer a useful tool for investigating the mechanism of selectivity of trabectedin, testing new combinations with this drug and evaluating novel therapies for myxoid liposarcoma.

• Authors: Roberta Frapolli, Elena Tamborini, Emanuela Virdis, Ezia Bello, Eva Tarantino, Sergio Marchini, Federica Grosso, Roberta Sanfilippo, Alessandro Gronchi, Juan Carlos Tercero, Gabriella Peloso, Paolo Casali, Silvana Pilotti, Maurizio D'Incalci
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 16 Issue 20 Pg. 4958-67 (Oct 15 2010) ISSN: 1557-3265 [Electronic] United States
• PMID: 20732964 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2010 AACR.

Chemical References

• Antineoplastic Agents, Alkylating
• Dioxoles
• Tetrahydroisoquinolines
• Trabectedin

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Antineoplastic Agents, Alkylating (pharmacology)
• Cell Growth Processes (physiology)
• Dioxoles (pharmacology)
• Female
• Humans
• In Situ Hybridization, Fluorescence
• Liposarcoma, Myxoid (drug therapy, genetics, pathology)
• Male
• Mice
• Mice, Nude
• Middle Aged
• Neoplasm Transplantation
• Reverse Transcriptase Polymerase Chain Reaction
• Tetrahydroisoquinolines (pharmacology)
• Trabectedin
• Transplantation, Heterologous (pathology)