Establishment and characterisation of a human clear cell sarcoma model in nude mice.
We have established a new experimental model of human clear cell sarcoma, UM-CCS1, using serial subcutaneous transplantation of intact tumour tissue in nude mice. The heterotransplanted nude mouse tumours retained characteristic morphological features of the primary clear cell sarcoma. Immunohistochemical analysis showed the retained expression patterns of S-100 protein, melanoma-associated antigen HMB-45 and vimentin in the xenografts as compared to the primary tumour. DNA index showed low variations both between the xenografts in the same passage and between the serial passages. Cytogenetic analysis of the primary tumour and the xenografts showed the unbalanced translocation der(6)t(6;12)(p23;q13). Based on the combined genetic data a reasonable interpretation of our findings is that there was a complex chromosomal rearrangement resulting in a cytogenetically cryptic EWS-ATF1 fusion gene. Analysis of cell kinetics using in vivo incorporation of iododeoxyuridine and flow cytometry showed generally short potential doubling time (T(pot)) of the xenografts. Volume doubling time showed low variations without correlation with T(pot). The retained phenotypic and genotypic characteristics of the primary tumour and the morphological and structural stability over time makes the model suitable for studies on the tumour biology and treatment of clear cell sarcoma.
Crnalic
Sead
S
Department of Orthopaedics, University Hospital, Umeå, Sweden.
Panagopoulos
Ioannis
I
Boquist
Lennart
L
Mandahl
Nils
N
Stenling
Roger
R
Löfvenberg
Richard
R
D051697:Activating Transcription Factor 1; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D048429:Cell Size; D003582:Cytogenetics; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034802:RNA-Binding Protein EWS / Q000235:genetics; D018227:Sarcoma, Clear Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics
D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors