Elevated plasma transforming growth factor-beta 1 levels in breast cancer patients decrease after surgical removal of the tumor
F M Kong, M S Anscher, T Murase, B D Abbott, J D Iglehart, R L Jirtle, F M Kong, M S Anscher, T Murase, B D Abbott, J D Iglehart, R L Jirtle
Abstract
Objective: The authors determined whether untreated breast cancer patients have elevated plasma levels of transforming growth factor-beta 1 (TGF-beta 1).
Summary background data: Increased plasma TGF-beta 1 levels recently were found after chemotherapy in patients with advanced breast cancer. However, it currently is unknown whether this elevation in plasma TGF-beta 1 is caused by chemotherapy-induced normal tissue damage or whether it results from the presence of the tumor.
Methods: An enzyme-linked immunosorbent assay was used to measure plasma TGF-beta 1 levels in 26 newly diagnosed breast cancer patients before and after definitive surgery. Patients were grouped by postoperative tumor status: 1) negative lymph nodes (group 1); 2) positive lymph nodes (group 2); and 3) overt residual disease (group 3). The site of TGF-beta 1 production in the tumors was localized by immunohistochemistry and in situ hybridization.
Results: Plasma TGF-beta 1 levels were elevated preoperatively in 81% of the patients; TGF-beta 2 and TGF-beta 3 were undetectable. The preoperative TGF-beta 1 levels in the three patient groups were similar; however, the postoperative plasma TGF-beta 1 levels differed by disease status. The mean plasma TGF-beta 1 level in group 1 (n = 12) normalized after surgery (19.3 +/- 3.2 vs. 5.5 +/- 1.0 ng/mL, p < 0.001). In contrast, the mean plasma TGF-beta 1 levels remained above normal in both group 2 (n = 9) and group 3 (n = 5) after surgery. Transforming growth factor-beta 1 expression was found to be preferentially increased in the tumor stroma.
Conclusions: Breast tumors result in increased plasma TGF-beta 1 levels in 81% of patients. After surgical removal of the primary tumor, the plasma TGF-beta 1 level normalizes in the majority of patients; persistently elevated levels correlate with the presence of lymph node metastases or overt residual tumor. These findings suggest that the usefulness of TGF-beta 1 as a potential plasma marker for breast tumors deserves further study.
References
- Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494-8
- Int J Radiat Oncol Biol Phys. 1994 Oct 15;30(3):671-6
- J Biol Chem. 1986 Sep 15;261(26):12362-7
- Cell. 1987 Feb 13;48(3):417-28
- Anticancer Res. 1987 Nov-Dec;7(6):1271-5
- Nature. 1988 Jul 21;334(6179):260-2
- J Cell Biol. 1989 Feb;108(2):653-60
- J Immunol. 1989 Mar 1;142(5):1536-41
- J Immunol. 1989 Sep 15;143(6):1868-74
- Cell. 1990 Jun 15;61(6):1121-35
- Cell. 1990 Jun 15;61(6):1147-55
- J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):795-803
- Ciba Found Symp. 1991;157:98-108; discussion 108-14
- Breast Cancer Res Treat. 1991 May;18 Suppl 1:S55-62
- Cancer Res. 1991 Sep 15;51(18):4978-85
- Mol Endocrinol. 1991 Aug;5(8):1120-8
- Teratology. 1992 Jan;45(1):35-53
- Crit Rev Oncol Hematol. 1992 Jan;12(1):1-23
- Eur J Cancer. 1992;28(2-3):641-4
- Eur J Cancer. 1992;28(2-3):700-5
- Cancer Res. 1992 Aug 1;52(15):4261-4
- Cancer Res. 1992 Sep 1;52(17):4719-23
- Science. 1992 Aug 28;257(5074):1258-61
- Cancer Res. 1992 Dec 15;52(24):6949-52
- Acta Pathol Jpn. 1992 Sep;42(9):645-50
- N Engl J Med. 1993 Jun 3;328(22):1592-8
- J Pathol. 1993 May;170(1):15-22
- Am J Pathol. 1993 Aug;143(2):381-9
- Cancer Res. 1993 Sep 1;53(17):3849-52
- Clin Exp Immunol. 1993 Oct;94(1):220-4
- Biochem Biophys Res Commun. 1994 Mar 15;199(2):772-9
- Cancer. 1994 May 1;73(9):2275-9
- Science. 1994 Jun 24;264(5167):1936-8
- Carcinogenesis. 1994 Aug;15(8):1473-8
- J Exp Med. 1986 May 1;163(5):1037-50
Source: PubMed