BACKGROUND: Transforming growth factor-beta (TGF-beta) is a multipotent growth factor affecting development, homeostasis, and tissue repair. In addition, increased expression of TGF-beta 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-beta 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-beta expression. RESULTS: Expression of one or more TGF-beta isoforms was found in all the osteosarcomas. Immunoreactivity for TGF-beta1 and TGF-beta3 generally was stronger than for TGF-beta2. 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-beta3, but not of TGF-beta2 or TGF-beta1, related to disease progression, such that there was a statistically significant decrease in the disease free interval as the immunoreactivity for TGF-beta3 increased. CONCLUSIONS: All osteosarcomas expressed TGF-beta in the cytoplasm of the tumor cells as well as in their extracellular stroma. The presence of TGF-beta in the endothelial and perivascular layers of small vessels in the tumor stroma suggests angiogenic activity of this growth factor. The expression of TGF-beta3 was correlated strongly with disease progression (P = 0.027). These data suggest that increased expression of TGF-beta isoforms, especially TGF-beta3, may play a role in osteosarcoma progression.
BACKGROUND:Transforming growth factor-beta (TGF-beta) is a multipotent growth factor affecting development, homeostasis, and tissue repair. In addition, increased expression of TGF-beta 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-beta isoforms were evaluated in 25 high grade humanosteosarcomas. The Cox proportional hazards models and Kaplan-Meier curves were calculated correlating disease free survival with TGF-beta expression. RESULTS: Expression of one or more TGF-beta isoforms was found in all the osteosarcomas. Immunoreactivity for TGF-beta1 and TGF-beta3 generally was stronger than for TGF-beta2. 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-beta3, but not of TGF-beta2 or TGF-beta1, related to disease progression, such that there was a statistically significant decrease in the disease free interval as the immunoreactivity for TGF-beta3 increased. CONCLUSIONS: All osteosarcomas expressed TGF-beta in the cytoplasm of the tumor cells as well as in their extracellular stroma. The presence of TGF-beta in the endothelial and perivascular layers of small vessels in the tumor stroma suggests angiogenic activity of this growth factor. The expression of TGF-beta3 was correlated strongly with disease progression (P = 0.027). These data suggest that increased expression of TGF-beta isoforms, especially TGF-beta3, may play a role in osteosarcoma progression.
Authors: Gaurav Luther; Richard Rames; Eric R Wagner; Gaohui Zhu; Qing Luo; Yang Bi; Stephanie H Kim; Jian-Li Gao; Enyi Huang; Ke Yang; Linyuan Wang; Xing Liu; Mi Li; Ning Hu; Yuxi Su; Xiaoji Luo; Liang Chen; Jinyong Luo; Rex C Haydon; Hue H Luu; Lan Zhou; Tong-Chuan He Journal: Trends Cancer Res Date: 2010
Authors: Arantzazu Alfranca; Lucia Martinez-Cruzado; Juan Tornin; Ander Abarrategi; Teresa Amaral; Enrique de Alava; Pablo Menendez; Javier Garcia-Castro; Rene Rodriguez Journal: Cell Mol Life Sci Date: 2015-05-03 Impact factor: 9.261
Authors: Bernd Kubista; Florian Klinglmueller; Martin Bilban; Martin Pfeiffer; Richard Lass; Alexander Giurea; Phillipp T Funovics; Cyril Toma; Martin Dominkus; Rainer Kotz; Theresia Thalhammer; Klemens Trieb; Teresa Zettl; Christian F Singer Journal: Int Orthop Date: 2010-03-26 Impact factor: 3.075
Authors: J Kleeff; H Friess; P Simon; S Susmallian; P Büchler; A Zimmermann; M W Büchler; M Korc Journal: Dig Dis Sci Date: 1999-09 Impact factor: 3.199
Authors: C Li; R Gardy; B K Seon; S E Duff; S Abdalla; A Renehan; S T O'Dwyer; N Haboubi; S Kumar Journal: Br J Cancer Date: 2003-05-06 Impact factor: 7.640