Expression of transforming growth factor beta and transforming growth factor beta receptors on AIDS-associated Kaposi's sarcoma.
Several humoral growth factors may contribute to the development and growth of AIDS-associated Kaposi's sarcoma (KS). They are either provided by chronically activated cells of the immune system or in an autocrine/paracrine manner by the neoplastic cells themselves. Transforming growth factor beta(TGF-beta) may directly enhance the growth of KS cells and tumor matrix formation. To mediate a signal both TGF-beta receptors type I and type II (TbetaR-I and TbetaR-II) have to be expressed. We investigated the expression of TGF-beta, TGF-beta receptors types I and II, and endoglin, a nonsignaling-type TbetaR-III, by means of immunohistochemistry on skin biopsies from patients with AIDS-related KS. We found that the TGF-beta ligand was expressed by KS cells in 9 of 11 samples. TbetaR-II was strongly expressed in 10 of 12 samples, but none of the investigated tumor samples stained for TbetaR-I. Endoglin was weakly expressed on all KS lesions and stained the endothelium of tumor-associated vessels in 92% of the samples. These findings show that most KS lesions have the ability to produce TGF-beta and that KS cells maintain a high expression of TbetaR-II in the absence of TbetaR-I, which may allow KS to escape growth inhibitory effects of endocrine or paracrine TGF-beta.
Ciernik
I F
IF
Simmons Cancer Center, Department of Dermatology, and Department of Pathology, University of Texas, Southwestern Medical Center, Dallas, Texas 75235-8593, USA.
Krayenbühl Ciernik
B H
BH
Cockerell
C J
CJ
Minna
J D
JD
Gazdar
A F
AF
Carbone
D P
DP
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D015703:Antigens, CD; D000071063:Endoglin; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1