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Erschienen in: Cancer Chemotherapy and Pharmacology 3/2008

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

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

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2008

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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.
Literatur
1.
2.
Zurück zum Zitat 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 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
3.
Zurück zum Zitat 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 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
4.
Zurück zum Zitat 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 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
5.
Zurück zum Zitat Brenneman DE, Spector AA (1974) Utilization of ascites plasma very low density lipoprotein triglycerides by Ehrlich cells. J Lipid Res 15:309–316PubMed Brenneman DE, Spector AA (1974) Utilization of ascites plasma very low density lipoprotein triglycerides by Ehrlich cells. J Lipid Res 15:309–316PubMed
6.
Zurück zum Zitat 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, 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
7.
Zurück zum Zitat 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 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
8.
Zurück zum Zitat 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 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
9.
Zurück zum Zitat Spector AA (1967) The importance of fatty acid in tumor nutrition. Cancer Res 27:1580–1586PubMed Spector AA (1967) The importance of fatty acid in tumor nutrition. Cancer Res 27:1580–1586PubMed
10.
Zurück zum Zitat Spector AA, Steinberg D (1965) The utilization of unesterified palmitate by Ehrlich ascites tumor cells. J Biol Chem 240:3747–3753PubMed Spector AA, Steinberg D (1965) The utilization of unesterified palmitate by Ehrlich ascites tumor cells. J Biol Chem 240:3747–3753PubMed
11.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4–6PubMedCrossRef Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4–6PubMedCrossRef
20.
Zurück zum Zitat 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 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.
Zurück zum Zitat Ferrara N, Alitalo K (1999) Clinical applications of angiogenic growth factors and their inhibitors. Nat Med 5:1359–1364PubMedCrossRef Ferrara N, Alitalo K (1999) Clinical applications of angiogenic growth factors and their inhibitors. Nat Med 5:1359–1364PubMedCrossRef
22.
Zurück zum Zitat Folkman J (1995) Seminars in medicine of the Beth Israel Hospital, Boston. N Engl J Med 333:1757–1763PubMedCrossRef Folkman J (1995) Seminars in medicine of the Beth Israel Hospital, Boston. N Engl J Med 333:1757–1763PubMedCrossRef
23.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
29.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Takasaki Y, Deng JS, Tan EM (1981) A nuclear antigen associated with cell proliferation and blast transformation. J Exp Med 154:1899–1909PubMedCrossRef Takasaki Y, Deng JS, Tan EM (1981) A nuclear antigen associated with cell proliferation and blast transformation. J Exp Med 154:1899–1909PubMedCrossRef
32.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat White PC, Mune T, Agarwal AK (1997) 11β-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocrine Rev 18:135–156CrossRef White PC, Mune T, Agarwal AK (1997) 11β-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocrine Rev 18:135–156CrossRef
37.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Eckel RH (1987) Adipose tissue lipoprotein lipase. In: Borensztajn J (ed) Lipoprotein lipase. Evener, Chicago, pp 79–132 Eckel RH (1987) Adipose tissue lipoprotein lipase. In: Borensztajn J (ed) Lipoprotein lipase. Evener, Chicago, pp 79–132
43.
Zurück zum Zitat Tarentino AL, Maley F (1974) Purification and properties of an endo-β-N-acetylglucosaminidase from Streptomyces griseus. J Biol Chem 249:811–817PubMed Tarentino AL, Maley F (1974) Purification and properties of an endo-β-N-acetylglucosaminidase from Streptomyces griseus. J Biol Chem 249:811–817PubMed
44.
Zurück zum Zitat Rimsza ME (1978) Complications of corticoid therapy. Am J Dis Child 132:806–810PubMed Rimsza ME (1978) Complications of corticoid therapy. Am J Dis Child 132:806–810PubMed
Metadaten
Titel
Effect of cortisol on cell proliferation and the expression of lipoprotein lipase and vascular endothelial growth factor in a human osteosarcoma cell line
verfasst von
Kenshi Sakayama
Naohiko Mashima
Teruki Kidani
Tatsuhiko Miyazaki
Haruyasu Yamamoto
Hiroshi Masuno
Publikationsdatum
01.03.2008
Verlag
Springer-Verlag
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 3/2008
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-007-0492-x

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