Transforming growth factor-beta1 circulates in normal human plasma and is unchanged in advanced metastatic breast cancer.
A method has been developed to determine true plasma transforming growth factor beta (TGF-beta) levels by using the platelet alpha granule-specific marker, platelet factor 4, to correct for the TGF-beta contributed by platelets degranulated ex vivo. TGF-beta levels were measured on acid-ethanol extracts of human plasma using isoform-specific sandwich enzyme-linked immunosorbent assays. Normal human subjects had 4.1 +/- 2.0 ng/ml TGF-beta1 (range, 2.0-12.0; n = 42), <0.2 ng/ml TGF-beta2, and <0.1 ng/ml TGF-beta3 in their plasma. There were no significant changes with age or with hormonal status, but any given individual showed fluctuations of up to 3-fold in measured plasma TGF-beta levels due to unknown factors. Of 28 patients with advanced metastatic breast cancer, 2 had greatly elevated TGF-beta1 levels, while the rest were in the normal range. The presence of physiologically significant levels of TGF-beta1 in the plasmas of normal human subjects may indicate previously unsuspected endocrine roles for this peptide, while TGF-beta2 and TGF-beta3 appear to act only in a local autocrine/paracrine fashion.
Wakefield
L M
LM
Laboratory of Chemoprevention and Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892-5055, USA.
Letterio
J J
JJ
Chen
T
T
Danielpour
D
D
Allison
R S
RS
Pai
L H
LH
Denicoff
A M
AM
Noone
M H
MH
Cowan
K H
KH
O'Shaughnessy
J A
JA
D000328:Adult; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010978:Platelet Factor 4 / Q000032:analysis; D017698:Postmenopause / Q000097:blood; D011247:Pregnancy; D017697:Premenopause / Q000097:blood; D020033:Protein Isoforms / Q000097:blood; D012016:Reference Values; D015203:Reproducibility of Results; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000378:metabolism
D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D010978:Platelet Factor 4