Expression of transforming growth factor-β (TGF-β) isoforms in osteosarcomas

TGF-β3 is related to disease progression

Peter Kloen, Mark C. Gebhardt, Antonio Perez-Atayde, Andrew Rosenberg, Dempsey S. Springfield, Leslie I. Gold, Henry J. Mankin

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

BACKGROUND. Transforming growth factor-β (TGF-β) is a multipotent growth factor affecting development, homeostasis, and tissue repair. In addition, increased expression of TGF-β has been reported in different malignancies, suggesting a role for this growth factor in tumorigenesis. METHODS. Using immunohistochemistry, the expression, prevalence, and distribution of TGF-β isoforms were evaluated in 25 high grade human osteosarcomas. The Cox proportional hazards models and Kaplan-Meier curves were calculated correlating disease free survival with TGF-β expression. RESULTS. Expression of one or more TGF-β isoforms was found in all the osteosarcomas. Immunoreactivity for TGF-β1 and TGF-β3 generally was stronger than for TGF-β2. The cytoplasm of the tumor cells showed stronger staining than their surrounding extracellular stroma. Most notably, osteoclasts showed strong to intense staining for all three isoforms. In 11 of 25 specimens angiogenic activity was noted with staining of multiple small vessels in the tumor stroma. Expression of TGF-β3, but not of TGF-β2 or TGF-β1, related to disease progression, such that there was a statistically significant decrease in the disease free interval as the immunoreactivity for TGF-β3 increased. CONCLUSIONS. All osteosarcomas expressed TGF-β in the cytoplasm of the tumor cells as well as in their extracellular stroma. The presence of TGF-β in the endothelial and perivascular layers of small vessels in the tumor stroma suggests angiogenic activity of this growth factor. The expression of TGF-β3 was correlated strongly with disease progression (P = 0.027). These data suggest that increased expression of TGF- β isoforms, especially TGF-β3, may play a role in osteosarcoma progression.

Original languageEnglish
Pages (from-to)2230-2239
Number of pages10
JournalCancer
Volume80
Issue number12
DOIs
StatePublished - Dec 15 1997
Externally publishedYes

Fingerprint

Transforming Growth Factors
Osteosarcoma
Disease Progression
Protein Isoforms
Intercellular Signaling Peptides and Proteins
Neoplasms
Staining and Labeling
Cytoplasm
Osteoclasts
Proportional Hazards Models

Keywords

  • Disease progression
  • Immunohistochemistry
  • Osteosarcoma
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression of transforming growth factor-β (TGF-β) isoforms in osteosarcomas : TGF-β3 is related to disease progression. / Kloen, Peter; Gebhardt, Mark C.; Perez-Atayde, Antonio; Rosenberg, Andrew; Springfield, Dempsey S.; Gold, Leslie I.; Mankin, Henry J.

In: Cancer, Vol. 80, No. 12, 15.12.1997, p. 2230-2239.

Research output: Contribution to journalArticle

Kloen, Peter ; Gebhardt, Mark C. ; Perez-Atayde, Antonio ; Rosenberg, Andrew ; Springfield, Dempsey S. ; Gold, Leslie I. ; Mankin, Henry J. / Expression of transforming growth factor-β (TGF-β) isoforms in osteosarcomas : TGF-β3 is related to disease progression. In: Cancer. 1997 ; Vol. 80, No. 12. pp. 2230-2239.
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abstract = "BACKGROUND. Transforming growth factor-β (TGF-β) is a multipotent growth factor affecting development, homeostasis, and tissue repair. In addition, increased expression of TGF-β has been reported in different malignancies, suggesting a role for this growth factor in tumorigenesis. METHODS. Using immunohistochemistry, the expression, prevalence, and distribution of TGF-β isoforms were evaluated in 25 high grade human osteosarcomas. The Cox proportional hazards models and Kaplan-Meier curves were calculated correlating disease free survival with TGF-β expression. RESULTS. Expression of one or more TGF-β isoforms was found in all the osteosarcomas. Immunoreactivity for TGF-β1 and TGF-β3 generally was stronger than for TGF-β2. The cytoplasm of the tumor cells showed stronger staining than their surrounding extracellular stroma. Most notably, osteoclasts showed strong to intense staining for all three isoforms. In 11 of 25 specimens angiogenic activity was noted with staining of multiple small vessels in the tumor stroma. Expression of TGF-β3, but not of TGF-β2 or TGF-β1, related to disease progression, such that there was a statistically significant decrease in the disease free interval as the immunoreactivity for TGF-β3 increased. CONCLUSIONS. All osteosarcomas expressed TGF-β in the cytoplasm of the tumor cells as well as in their extracellular stroma. The presence of TGF-β in the endothelial and perivascular layers of small vessels in the tumor stroma suggests angiogenic activity of this growth factor. The expression of TGF-β3 was correlated strongly with disease progression (P = 0.027). These data suggest that increased expression of TGF- β isoforms, especially TGF-β3, may play a role in osteosarcoma progression.",
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AU - Kloen, Peter

AU - Gebhardt, Mark C.

AU - Perez-Atayde, Antonio

AU - Rosenberg, Andrew

AU - Springfield, Dempsey S.

AU - Gold, Leslie I.

AU - Mankin, Henry J.

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N2 - BACKGROUND. Transforming growth factor-β (TGF-β) is a multipotent growth factor affecting development, homeostasis, and tissue repair. In addition, increased expression of TGF-β has been reported in different malignancies, suggesting a role for this growth factor in tumorigenesis. METHODS. Using immunohistochemistry, the expression, prevalence, and distribution of TGF-β isoforms were evaluated in 25 high grade human osteosarcomas. The Cox proportional hazards models and Kaplan-Meier curves were calculated correlating disease free survival with TGF-β expression. RESULTS. Expression of one or more TGF-β isoforms was found in all the osteosarcomas. Immunoreactivity for TGF-β1 and TGF-β3 generally was stronger than for TGF-β2. The cytoplasm of the tumor cells showed stronger staining than their surrounding extracellular stroma. Most notably, osteoclasts showed strong to intense staining for all three isoforms. In 11 of 25 specimens angiogenic activity was noted with staining of multiple small vessels in the tumor stroma. Expression of TGF-β3, but not of TGF-β2 or TGF-β1, related to disease progression, such that there was a statistically significant decrease in the disease free interval as the immunoreactivity for TGF-β3 increased. CONCLUSIONS. All osteosarcomas expressed TGF-β in the cytoplasm of the tumor cells as well as in their extracellular stroma. The presence of TGF-β in the endothelial and perivascular layers of small vessels in the tumor stroma suggests angiogenic activity of this growth factor. The expression of TGF-β3 was correlated strongly with disease progression (P = 0.027). These data suggest that increased expression of TGF- β isoforms, especially TGF-β3, may play a role in osteosarcoma progression.

AB - BACKGROUND. Transforming growth factor-β (TGF-β) is a multipotent growth factor affecting development, homeostasis, and tissue repair. In addition, increased expression of TGF-β has been reported in different malignancies, suggesting a role for this growth factor in tumorigenesis. METHODS. Using immunohistochemistry, the expression, prevalence, and distribution of TGF-β isoforms were evaluated in 25 high grade human osteosarcomas. The Cox proportional hazards models and Kaplan-Meier curves were calculated correlating disease free survival with TGF-β expression. RESULTS. Expression of one or more TGF-β isoforms was found in all the osteosarcomas. Immunoreactivity for TGF-β1 and TGF-β3 generally was stronger than for TGF-β2. The cytoplasm of the tumor cells showed stronger staining than their surrounding extracellular stroma. Most notably, osteoclasts showed strong to intense staining for all three isoforms. In 11 of 25 specimens angiogenic activity was noted with staining of multiple small vessels in the tumor stroma. Expression of TGF-β3, but not of TGF-β2 or TGF-β1, related to disease progression, such that there was a statistically significant decrease in the disease free interval as the immunoreactivity for TGF-β3 increased. CONCLUSIONS. All osteosarcomas expressed TGF-β in the cytoplasm of the tumor cells as well as in their extracellular stroma. The presence of TGF-β in the endothelial and perivascular layers of small vessels in the tumor stroma suggests angiogenic activity of this growth factor. The expression of TGF-β3 was correlated strongly with disease progression (P = 0.027). These data suggest that increased expression of TGF- β isoforms, especially TGF-β3, may play a role in osteosarcoma progression.

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KW - Immunohistochemistry

KW - Osteosarcoma

KW - Transforming growth factor-β

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