Top

Cancer Chemotherapy and Pharmacology

Published in:

01-03-2008 | Original Article

Effect of cortisol on cell proliferation and the expression of lipoprotein lipase and vascular endothelial growth factor in a human osteosarcoma cell line

Authors: Kenshi Sakayama, Naohiko Mashima, Teruki Kidani, Tatsuhiko Miyazaki, Haruyasu Yamamoto, Hiroshi Masuno

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2008

Abstract

Purpose

The aim of this study is to investigate whether cortisol inhibited cell proliferation and the expressions of lipoprotein lipase (LPL), a key enzyme involved in the energy metabolism in tumor cells, and vascular endothelial growth factor (VEGF), a potent angiogenic factor in the tumor, in cultures of OST cells, a human osteosarcoma cell line.

Methods

OST cells were treated for 48 h with or without cortisol. To examine the effect of cortisol on cell proliferation, the expression of proliferating cell nuclear antigen (PCNA) was examined by Western blotting, and the amount of ³H-thymidine incorporated into DNA during the last 30 min of the 48-h treatment period was measured. To examine the effect of cortisol on the expression of LPL, the activity and mass of LPL were measured in the extract of acetone/ether powder of cells, and the amount of ³⁵S-methionine incorporated into LPL during the last 2 h of the 48-h treatment period was measured by immunoprecipitation. The expression of VEGF was examined by immunohistochemistry and Western blotting.

Results

The amount of ³H-thymidine incorporated into DNA and the level of PCNA were lower in the cortisol-treated cultures than in the untreated cultures, thus indicating that cortisol inhibited the proliferation of OST cells. The synthetic rate and activity of LPL were lower in the cortisol-treated cultures than in the untreated cultures but no difference in the specific activity of LPL between the two cultures was observed, thus indicating that cortisol inhibited LPL synthesis, thereby resulting in a decreased LPL activity. The expression of VEGF was lower in the cortisol-treated cultures than in the untreated cultures.

Conclusion

Cortisol not only has the ability to inhibit cell proliferation but also the ability to inhibit the expressions of LPL and VEGF in cultures of OST cells.

Ferguson WS, Goorin AM (2001) Current treatment of osteosarcoma. Cancer Invest 19:292–315PubMedCrossRef

Rogatsky I, Hittelman AB, Pearce D, Garabedian MJ (1999) Distinct glucocorticoid receptor transcriptional regulatory surfaces mediate the cytotoxic and cytostatic effects of glucocorticoids. Mol Cell Biol 19:5036–5049PubMed

Song LN (1994) Effects of retinoic acid and dexamethasone on proliferation, differentiation, and glucocorticoid receptor expression in cultured human osteosarcoma cells. Oncol Res 6:111–118PubMed

Kudawara I, Ueda T, Yoshikawa H, Miyama T, Yamamoto T, Nishizawa Y (2001) In vivo inhibition of tumor growth by dexamethasone in murine osteosarcoma. Eur J Cancer 37:1703–1708PubMedCrossRef

Brenneman DE, Spector AA (1974) Utilization of ascites plasma very low density lipoprotein triglycerides by Ehrlich cells. J Lipid Res 15:309–316PubMed

Medes G, Paden G, Weinhouse S (1957) Metabolism of neoplastic tissues. XI. Absorption and oxidation of dietary fatty acids by implanted tumors. Cancer Res 17:127–133PubMed

Medes G, Weinhouse S (1958) Metabolism of neoplastic tissue. XIII. Substrate competition in fatty acid oxidation in ascites tumor cells. Cancer Res 18:352–359PubMed

Sakayama K, Masuno H, Okumura H, Shibata T, Okuda H (1996) Recombinant human tumor necrosis factor-α suppresses synthesis, activity and secretion of lipoprotein lipase in cultures of a human osteosarcoma cell line. Biochem J 316:813–817PubMed

Spector AA (1967) The importance of fatty acid in tumor nutrition. Cancer Res 27:1580–1586PubMed

10.

Spector AA, Steinberg D (1965) The utilization of unesterified palmitate by Ehrlich ascites tumor cells. J Biol Chem 240:3747–3753PubMed

11.

Sakayama K, Masuno H, Miyazaki T, Okumura H, Shibata T, Okuda H (1994) Existence of lipoprotein lipase in human sarcomas and carcinomas. Jpn J Cancer Res 85:515–521PubMed

12.

Bagdade JD, Yee E, Albers J, Pykalisto OJ (1976) Glococorticoids and triglyceride transport: effect on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rats. Metabolism 25:533–542PubMedCrossRef

13.

Kidani T, Sakayama K, Masuno H, Takubo N, Matsuda Y, Okuda H, Yamamoto H (2002) Active-dimeric form of lipoprotein lipase increases in the adipose tissue of patients with rheumatoid arthritis treated with prednisolone. Biochim Biophys Acta 1584:31–36PubMed

14.

Krotkiewski M, Bjorntorp P, Smith U (1976) The effect of long-term dexamethasone treatment on lipoprotein lipase activity in rat fat cells. Horm Metab Res 8:245–246PubMedCrossRef

15.

Ong JM, Simsolo RB, Saffari B, Kern PA (1992) The regulation of lipoprotein lipase gene expression by dexamethasone in isolated rat adipocytes. Endocrinology 130:2310–2316PubMedCrossRef

16.

Ottosson M, Marin P, Karason K, Elander A, Bjorntorp P (1995) Blockade of the glucocorticoid receptor with RU 486: effects of in vitro and in vivo on human adipose tissue lipoprotein lipase activity. Obes Res 3:233–240PubMed

17.

Sakayama K, Masuno H, Kidani T, Matsuda Y, Yamamoto H, Okuda H (2001) Synthesis of active high mannose-type lipoprotein lipase in human adipose tissues. Atherosclerosis 155:29–35PubMedCrossRef

18.

Taskinen M-R, Kuusi T, Yki-Javinen H, Nikkila EA (1998) Short-term effects of prednisone on serum lipids and high density lipoprotein fractions in normolipidemic healthy men. J Clin Endocrinol Metab 67:291–299CrossRef

19.

Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4–6PubMedCrossRef

20.

Chao C, Al-Saleem T, Brooks JJ, Rogatko A, Kraybill WG, Eisenberg B (2001) Vascular endothelial growth factor and soft tissue sarcomas: tumor expression correlates with grade. Ann Surg Oncol 8:260–267PubMedCrossRef

21.

Ferrara N, Alitalo K (1999) Clinical applications of angiogenic growth factors and their inhibitors. Nat Med 5:1359–1364PubMedCrossRef

22.

Folkman J (1995) Seminars in medicine of the Beth Israel Hospital, Boston. N Engl J Med 333:1757–1763PubMedCrossRef

23.

Kaya M, Wada K, Akatsuka T, Kawaguchi S, Nagoya S, Shindoh M, Higashino F, Mezawa F, Okada F, Ishii S (2000) Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res 6:572–577PubMed

24.

Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844PubMedCrossRef

25.

Sawaoka H, Tsuji S, Tsujii M, Gunawan ES, Sasaki Y, Kawano S, Hori M (1999) Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Lab Invest 79:1469–1477PubMed

26.

Sakayama K, Kidani T, Miyazaki T, Shirakata H, Kimura Y, Kamogawa J, Masuno H, Yamamoto H (2004) Effect of ketoprofen in topical formulation on vascular endothelial growth factor expression and tumor growth in nude mice with osteosarcoma. J Orthop Res 22:1168–1174PubMedCrossRef

27.

Smulson ME, Kang VH, Ntambi JM, Rosenthal DS, Ding R, Simbulan CM (1995) Requirement for the expression of poly(ADP-ribose)polymerase during the early stages of differentiation of 3T3-L1 preadipocytes, as studies by antisense RNA induction. J Biol Chem 270:119–127PubMedCrossRef

28.

Hinegardner RT (1971) An improved fluorometric assay for DNA. Anal Biochem 39:197–201PubMedCrossRef

29.

Masuno H, Blanchette-Mackie EJ, Chernick SS, Scow RO (1990) Synthesis of inactive nonsecretable high mannose-type lipoprotein lipase by cultured brown adipocytes of combined lipase deficient cld/cld mice. J Biol Chem 265:1628–1638PubMed

30.

Celis JE, Celis E (1985) Cell cycle-dependent variations in the distribution of the nuclear proprotein cyclin proliferating cell nuclear antigen in cultured cells: subdivision of S phase. Proc Natl Acad Sci USA 82:3262–3266PubMedCrossRef

31.

Takasaki Y, Deng JS, Tan EM (1981) A nuclear antigen associated with cell proliferation and blast transformation. J Exp Med 154:1899–1909PubMedCrossRef

32.

Matsuno Y, Hirohashi S, Furuya S, Sakamoto M, Mukai K, Shimosato Y (1990) Heterogeneity of proliferative activity in nodule-in-nodule lesions of small hepatocellular carcinoma. Jpn J Cancer Res 81:1137–1140PubMed

33.

Robbins BA, de la Vega D, Ogata K, Tan EM, Nakamura RM (1987) Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies. Arch Pathol Lab Med 111:841–845PubMed

34.

Sun K, He P, Yang K (2002) Intracrine induction of 11β-hydroxysteroid dehydrogenase type 1 expression by glucocorticoid potentiates prostaglandin production in the human chorionic trophoblast. Biol Reprod 67:1450–1455PubMedCrossRef

35.

van Beek JP, Guan H, Julan L, Yang K (2004) Glucocorticoids stimulate the expression of 11β-hydroxysteroid dehydrogenase type 2 in cultured human placental trophoblast cells. J Clin Endocrinol Metab 89:5614–5621PubMedCrossRef

36.

White PC, Mune T, Agarwal AK (1997) 11β-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocrine Rev 18:135–156CrossRef

37.

Steffen M, Scherdin U, Duvigneau C, Holzel F (1988) Glucocorticoid-induced alterations of morphology and growth of fibrosarcoma cells derived from 7,12-dimethylbenz(a)anthracene rat mammary tumor. Cancer Res 48:7212–7218PubMed

38.

Walker MJ, Lim C, Das Gupta TK, Beattie CW (1986) Effects of glucocorticoid on the growth of human fibrosarcoma cell line HT-1080. Cancer Res 46:4927–4932PubMed

39.

Braunschweiger PG, Schiffer LM (1981) Antiproliferative effects of corticosteroids in C3H/HeJ mammary tumors and implications for sequential combination chemotherapy. Cancer Res 41:3324–3330PubMed

40.

Posner JB, Howieson J, Cvitkovic E (1977) “Disappearing” spinal cord compression: oncolytic effect of glucocorticoid (and other chemotherapeutic agents) on epidural metastases. Ann Neurol 2:409–413PubMedCrossRef

41.

Madsen WE, Das Gupta TK, Walker MJ (1989) The influence of glucocorticoids on the growth of a human leiomyosarcoma cell line SK-LMS-1. Int J Cancer 44:1034–1040PubMedCrossRef

42.

Eckel RH (1987) Adipose tissue lipoprotein lipase. In: Borensztajn J (ed) Lipoprotein lipase. Evener, Chicago, pp 79–132

43.

Tarentino AL, Maley F (1974) Purification and properties of an endo-β-N-acetylglucosaminidase from Streptomyces griseus. J Biol Chem 249:811–817PubMed

44.

Rimsza ME (1978) Complications of corticoid therapy. Am J Dis Child 132:806–810PubMed

Title: Effect of cortisol on cell proliferation and the expression of lipoprotein lipase and vascular endothelial growth factor in a human osteosarcoma cell line
Authors: Kenshi Sakayama
Naohiko Mashima
Teruki Kidani
Tatsuhiko Miyazaki
Haruyasu Yamamoto
Hiroshi Masuno
Publication date: 01-03-2008
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2008
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-007-0492-x

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2008

Consequences of increased vascular permeability induced by treatment of mice with 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and thalidomide

Phase II trial of gemcitabine and irinotecan in previously treated patients with small-cell lung cancer

Phase I dose-finding and pharmacokinetic study of the oral epidermal growth factor receptor tyrosine kinase inhibitor Ro50-8231 (erlotinib) in Japanese patients with solid tumors

Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL

A small molecule pan-Bcl-2 family inhibitor, GX15-070, induces apoptosis and enhances cisplatin-induced apoptosis in non-small cell lung cancer cells

Glut-1 as a therapeutic target: increased chemoresistance and HIF-1-independent link with cell turnover is revealed through COMPARE analysis and metabolomic studies

Keynote webinar | Spotlight on antibody–drug conjugates in cancer