Cargando…

Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

BACKGROUND: Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been...

Descripción completa

Detalles Bibliográficos
Autores principales: Kodama, Atsushi, Sakai, Hiroki, Matsuura, Satoko, Murakami, Mami, Murai, Atsuko, Mori, Takashi, Maruo, Kouji, Kimura, Tohru, Masegi, Toshiaki, Yanai, Tokuma
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768746/
https://www.ncbi.nlm.nih.gov/pubmed/19825192
http://dx.doi.org/10.1186/1471-2407-9-363
_version_ 1782173503295848448
author Kodama, Atsushi
Sakai, Hiroki
Matsuura, Satoko
Murakami, Mami
Murai, Atsuko
Mori, Takashi
Maruo, Kouji
Kimura, Tohru
Masegi, Toshiaki
Yanai, Tokuma
author_facet Kodama, Atsushi
Sakai, Hiroki
Matsuura, Satoko
Murakami, Mami
Murai, Atsuko
Mori, Takashi
Maruo, Kouji
Kimura, Tohru
Masegi, Toshiaki
Yanai, Tokuma
author_sort Kodama, Atsushi
collection PubMed
description BACKGROUND: Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. METHODS: Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets. RESULTS: Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors. CONCLUSION: We established 6 xenograft canine HSA tumors in nude mice and found that the expressions of angiogenic growth factors and their receptors in xenograft HSAs were similar to those in spontaneous HSA. Furthermore, we detected the expression of angiogenic homeobox genes; therefore, xenograft models may be useful in analyzing malignant growth in HSA.
format Text
id pubmed-2768746
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-27687462009-10-28 Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes Kodama, Atsushi Sakai, Hiroki Matsuura, Satoko Murakami, Mami Murai, Atsuko Mori, Takashi Maruo, Kouji Kimura, Tohru Masegi, Toshiaki Yanai, Tokuma BMC Cancer Research Article BACKGROUND: Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. METHODS: Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets. RESULTS: Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors. CONCLUSION: We established 6 xenograft canine HSA tumors in nude mice and found that the expressions of angiogenic growth factors and their receptors in xenograft HSAs were similar to those in spontaneous HSA. Furthermore, we detected the expression of angiogenic homeobox genes; therefore, xenograft models may be useful in analyzing malignant growth in HSA. BioMed Central 2009-10-14 /pmc/articles/PMC2768746/ /pubmed/19825192 http://dx.doi.org/10.1186/1471-2407-9-363 Text en Copyright ©2009 Kodama et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kodama, Atsushi
Sakai, Hiroki
Matsuura, Satoko
Murakami, Mami
Murai, Atsuko
Mori, Takashi
Maruo, Kouji
Kimura, Tohru
Masegi, Toshiaki
Yanai, Tokuma
Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes
title Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes
title_full Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes
title_fullStr Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes
title_full_unstemmed Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes
title_short Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes
title_sort establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768746/
https://www.ncbi.nlm.nih.gov/pubmed/19825192
http://dx.doi.org/10.1186/1471-2407-9-363
work_keys_str_mv AT kodamaatsushi establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes
AT sakaihiroki establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes
AT matsuurasatoko establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes
AT murakamimami establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes
AT muraiatsuko establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes
AT moritakashi establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes
AT maruokouji establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes
AT kimuratohru establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes
AT masegitoshiaki establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes
AT yanaitokuma establishmentofcaninehemangiosarcomaxenograftmodelsexpressingendothelialgrowthfactorstheirreceptorsandangiogenesisassociatedhomeoboxgenes