PMID- 2054795
OWN - NLM
STAT- MEDLINE
DCOM- 19910801
LR  - 20041117
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 51
IP  - 13
DP  - 1991 Jul 1
TI  - Transforming growth factor beta 1 induces cachexia and systemic fibrosis without 
      an antitumor effect in nude mice.
PG  - 3590-4
AB  - While stimulating the growth of fibroblasts, transforming growth factor beta 1 
      (TGF-beta 1) inhibits the growth of various normal and malignant cell lines in 
      vitro. We studied the effects of TGF-beta 1 in vivo. The level of TGF-beta 1 in 
      serum was maximally elevated 2 h after injecting 1 muCi of 125I-TGF-beta 1 into 
      the peritoneal cavity of nude mice. Five h after the i.p. administration of 10 
      micrograms of unlabeled TGF-beta 1, 20 ng/ml of TGF-beta-like material in serum 
      were detected by a radioreceptor assay on A549 lung carcinoma cells. 
      Trichloracetic acid-precipitable 125I-TGF-beta 1 was taken up by liver, spleen, 
      lungs, kidneys, and tumor tissue but not by the brain. At doses exceeding 2 
      micrograms/day, TGF-beta 1 induced a generalized interstitial fibrosis and a 
      cachexia, which was not mediated by elevated serum levels of tumor necrosis 
      factor alpha as determined by Western blot analysis and enzyme-linked 
      immunosorbent assay. A total of 200,000 cells of the estrogen receptor-negative 
      human breast cancer line MDA-MB-231, which had been shown to be maximally growth 
      inhibited in vitro by 40 pM TGF-beta 1 and to have high-affinity receptors (9, 
      11, 12), were injected into the mammary fat pad of each nude mouse. The duration 
      of treatment was 16 days with ten animals in the control group and five animals 
      in the treated groups. The dose ranged from 1 to 4 micrograms per animal daily. 
      The treatment was started 24 h after the injection of the tumor cells. Tumor 
      growth was not significantly affected at either nontoxic or toxic doses of 
      TGF-beta 1. Thus, we have demonstrated that TGF-beta 1, apart from being a local 
      growth factor, has systemic effects, such as cachexia and multiple fibrosis. Its 
      role as an antitumor agent may be limited.
FAU - Zugmaier, G
AU  - Zugmaier G
AD  - Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 
      20007.
FAU - Paik, S
AU  - Paik S
FAU - Wilding, G
AU  - Wilding G
FAU - Knabbe, C
AU  - Knabbe C
FAU - Bano, M
AU  - Bano M
FAU - Lupu, R
AU  - Lupu R
FAU - Deschauer, B
AU  - Deschauer B
FAU - Simpson, S
AU  - Simpson S
FAU - Dickson, R B
AU  - Dickson RB
FAU - Lippman, M
AU  - Lippman M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/*pathology
MH  - Cachexia/*chemically induced
MH  - Cell Division/drug effects
MH  - Fibrosis/*chemically induced
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Organ Size/drug effects
MH  - Transforming Growth Factor beta/pharmacokinetics/*pharmacology/toxicity
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
EDAT- 1991/07/01 00:00
MHDA- 1991/07/01 00:01
CRDT- 1991/07/01 00:00
PHST- 1991/07/01 00:00 [pubmed]
PHST- 1991/07/01 00:01 [medline]
PHST- 1991/07/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1991 Jul 1;51(13):3590-4.