Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma

Mohamed Abou-Shady, Hans U. Baer, Helmut Friess, Pascal Berberat, Arthur Zimmermann, Hans Graber, Leslie I. Gold, Murray Korc, Markus W. Büchler

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

BACKGROUND: Transforming growth factor betas (TGF-βs) are multifunctional polypeptides that have been suggested to influence tumor growth. They mediate their functions via specific cell surface receptors (type I ALK5 and type II TGF-β receptors). The aim of this study was to analyze the roles of the three TGF-βs and their signaling receptors in human hepatocellular carcinoma (HCC). METHODS: HCC tissue samples were obtained from 18 patients undergoing partial liver resection. Normal liver tissues from 7 females and 3 males served as controls. The tissues for histological analysis were fixed in Bouin's solution and paraffin embedded. For RNA analysis, freshly obtained tissue samples were snap frozen in liquid nitrogen and stored at -80°C until used. Northern blot analysis was used in normal liver and HCC to examine the expression of TGF-β1, -β2, -β3 and their receptors: type I ALK5 (TβR-I ALK5), type II (TβR-II), and type III (TβR- III). Immunohistochemistry was performed to localize the corresponding proteins. RESULTS: All three TGF-βs demonstrated a marked mRNA overexpression in HCC in comparison with normal controls, whereas the levels of all three TGF-β receptors showed no significant changes. Intense TGF- β1, TGF-β2, and TGF-β3 immunostaining was found in hepatocellular carcinoma cells and in the perineoplastic stroma with immunohistochemistry, whereas no or mild immunostaining was present in the normal liver. For TβR- I ALK5 and TβR-II, the immunostaining in both HCC and normal liver was mild to moderate, with a slightly higher intensity in the normal tissues. CONCLUSION: The upregulation of TGF-βs in HCC suggests an important role for these isoforms in hepatic carcinogenesis and tumor progression. Moreover, the localization of the immunoreactivity in both malignant hepatocytes and stromal cells suggests that TGF-βs act via autocrine and paracrine pathways in this neoplasm.

Original languageEnglish (US)
Pages (from-to)209-215
Number of pages7
JournalAmerican Journal of Surgery
Volume177
Issue number3
DOIs
StatePublished - Mar 1999
Externally publishedYes

Fingerprint

Transforming Growth Factor beta
Hepatocellular Carcinoma
Liver
Immunohistochemistry
Neoplasms
Cell Surface Receptors
Stromal Cells
Northern Blotting
Paraffin
Hepatocytes
Protein Isoforms
Carcinogenesis
Up-Regulation
Nitrogen
RNA
Messenger RNA
Peptides
Growth
Proteins

ASJC Scopus subject areas

  • Surgery

Cite this

Abou-Shady, M., Baer, H. U., Friess, H., Berberat, P., Zimmermann, A., Graber, H., ... Büchler, M. W. (1999). Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma. American Journal of Surgery, 177(3), 209-215. https://doi.org/10.1016/S0002-9610(99)00012-4

Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma. / Abou-Shady, Mohamed; Baer, Hans U.; Friess, Helmut; Berberat, Pascal; Zimmermann, Arthur; Graber, Hans; Gold, Leslie I.; Korc, Murray; Büchler, Markus W.

In: American Journal of Surgery, Vol. 177, No. 3, 03.1999, p. 209-215.

Research output: Contribution to journalArticle

Abou-Shady, M, Baer, HU, Friess, H, Berberat, P, Zimmermann, A, Graber, H, Gold, LI, Korc, M & Büchler, MW 1999, 'Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma', American Journal of Surgery, vol. 177, no. 3, pp. 209-215. https://doi.org/10.1016/S0002-9610(99)00012-4
Abou-Shady, Mohamed ; Baer, Hans U. ; Friess, Helmut ; Berberat, Pascal ; Zimmermann, Arthur ; Graber, Hans ; Gold, Leslie I. ; Korc, Murray ; Büchler, Markus W. / Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma. In: American Journal of Surgery. 1999 ; Vol. 177, No. 3. pp. 209-215.
@article{c7dfc605687a4225b6ec0634137fc841,
title = "Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma",
abstract = "BACKGROUND: Transforming growth factor betas (TGF-βs) are multifunctional polypeptides that have been suggested to influence tumor growth. They mediate their functions via specific cell surface receptors (type I ALK5 and type II TGF-β receptors). The aim of this study was to analyze the roles of the three TGF-βs and their signaling receptors in human hepatocellular carcinoma (HCC). METHODS: HCC tissue samples were obtained from 18 patients undergoing partial liver resection. Normal liver tissues from 7 females and 3 males served as controls. The tissues for histological analysis were fixed in Bouin's solution and paraffin embedded. For RNA analysis, freshly obtained tissue samples were snap frozen in liquid nitrogen and stored at -80°C until used. Northern blot analysis was used in normal liver and HCC to examine the expression of TGF-β1, -β2, -β3 and their receptors: type I ALK5 (TβR-I ALK5), type II (TβR-II), and type III (TβR- III). Immunohistochemistry was performed to localize the corresponding proteins. RESULTS: All three TGF-βs demonstrated a marked mRNA overexpression in HCC in comparison with normal controls, whereas the levels of all three TGF-β receptors showed no significant changes. Intense TGF- β1, TGF-β2, and TGF-β3 immunostaining was found in hepatocellular carcinoma cells and in the perineoplastic stroma with immunohistochemistry, whereas no or mild immunostaining was present in the normal liver. For TβR- I ALK5 and TβR-II, the immunostaining in both HCC and normal liver was mild to moderate, with a slightly higher intensity in the normal tissues. CONCLUSION: The upregulation of TGF-βs in HCC suggests an important role for these isoforms in hepatic carcinogenesis and tumor progression. Moreover, the localization of the immunoreactivity in both malignant hepatocytes and stromal cells suggests that TGF-βs act via autocrine and paracrine pathways in this neoplasm.",
author = "Mohamed Abou-Shady and Baer, {Hans U.} and Helmut Friess and Pascal Berberat and Arthur Zimmermann and Hans Graber and Gold, {Leslie I.} and Murray Korc and B{\"u}chler, {Markus W.}",
year = "1999",
month = "3",
doi = "10.1016/S0002-9610(99)00012-4",
language = "English (US)",
volume = "177",
pages = "209--215",
journal = "American Journal of Surgery",
issn = "0002-9610",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Transforming growth factor betas and their signaling receptors in human hepatocellular carcinoma

AU - Abou-Shady, Mohamed

AU - Baer, Hans U.

AU - Friess, Helmut

AU - Berberat, Pascal

AU - Zimmermann, Arthur

AU - Graber, Hans

AU - Gold, Leslie I.

AU - Korc, Murray

AU - Büchler, Markus W.

PY - 1999/3

Y1 - 1999/3

N2 - BACKGROUND: Transforming growth factor betas (TGF-βs) are multifunctional polypeptides that have been suggested to influence tumor growth. They mediate their functions via specific cell surface receptors (type I ALK5 and type II TGF-β receptors). The aim of this study was to analyze the roles of the three TGF-βs and their signaling receptors in human hepatocellular carcinoma (HCC). METHODS: HCC tissue samples were obtained from 18 patients undergoing partial liver resection. Normal liver tissues from 7 females and 3 males served as controls. The tissues for histological analysis were fixed in Bouin's solution and paraffin embedded. For RNA analysis, freshly obtained tissue samples were snap frozen in liquid nitrogen and stored at -80°C until used. Northern blot analysis was used in normal liver and HCC to examine the expression of TGF-β1, -β2, -β3 and their receptors: type I ALK5 (TβR-I ALK5), type II (TβR-II), and type III (TβR- III). Immunohistochemistry was performed to localize the corresponding proteins. RESULTS: All three TGF-βs demonstrated a marked mRNA overexpression in HCC in comparison with normal controls, whereas the levels of all three TGF-β receptors showed no significant changes. Intense TGF- β1, TGF-β2, and TGF-β3 immunostaining was found in hepatocellular carcinoma cells and in the perineoplastic stroma with immunohistochemistry, whereas no or mild immunostaining was present in the normal liver. For TβR- I ALK5 and TβR-II, the immunostaining in both HCC and normal liver was mild to moderate, with a slightly higher intensity in the normal tissues. CONCLUSION: The upregulation of TGF-βs in HCC suggests an important role for these isoforms in hepatic carcinogenesis and tumor progression. Moreover, the localization of the immunoreactivity in both malignant hepatocytes and stromal cells suggests that TGF-βs act via autocrine and paracrine pathways in this neoplasm.

AB - BACKGROUND: Transforming growth factor betas (TGF-βs) are multifunctional polypeptides that have been suggested to influence tumor growth. They mediate their functions via specific cell surface receptors (type I ALK5 and type II TGF-β receptors). The aim of this study was to analyze the roles of the three TGF-βs and their signaling receptors in human hepatocellular carcinoma (HCC). METHODS: HCC tissue samples were obtained from 18 patients undergoing partial liver resection. Normal liver tissues from 7 females and 3 males served as controls. The tissues for histological analysis were fixed in Bouin's solution and paraffin embedded. For RNA analysis, freshly obtained tissue samples were snap frozen in liquid nitrogen and stored at -80°C until used. Northern blot analysis was used in normal liver and HCC to examine the expression of TGF-β1, -β2, -β3 and their receptors: type I ALK5 (TβR-I ALK5), type II (TβR-II), and type III (TβR- III). Immunohistochemistry was performed to localize the corresponding proteins. RESULTS: All three TGF-βs demonstrated a marked mRNA overexpression in HCC in comparison with normal controls, whereas the levels of all three TGF-β receptors showed no significant changes. Intense TGF- β1, TGF-β2, and TGF-β3 immunostaining was found in hepatocellular carcinoma cells and in the perineoplastic stroma with immunohistochemistry, whereas no or mild immunostaining was present in the normal liver. For TβR- I ALK5 and TβR-II, the immunostaining in both HCC and normal liver was mild to moderate, with a slightly higher intensity in the normal tissues. CONCLUSION: The upregulation of TGF-βs in HCC suggests an important role for these isoforms in hepatic carcinogenesis and tumor progression. Moreover, the localization of the immunoreactivity in both malignant hepatocytes and stromal cells suggests that TGF-βs act via autocrine and paracrine pathways in this neoplasm.

UR - http://www.scopus.com/inward/record.url?scp=0032964644&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032964644&partnerID=8YFLogxK

U2 - 10.1016/S0002-9610(99)00012-4

DO - 10.1016/S0002-9610(99)00012-4

M3 - Article

VL - 177

SP - 209

EP - 215

JO - American Journal of Surgery

JF - American Journal of Surgery

SN - 0002-9610

IS - 3

ER -