Multiple effects of alpha(1)-antitrypsin on breast carcinoma MDA-MB 468 cell growth and invasiveness
(2003) In European Journal of Cancer Prevention 12(2). p.117-124- Abstract
- The degradation of extracellular matrix during cancer invasion results from the action of several protease and protease inhibitor systems. alpha(1)-Antitrypsin (AAT) is a serine proteinase inhibitor produced by various tumour cells, and its plasma concentration rises during inflammation, infection and malignant diseases. AAT is found in a native, inhibitory active form, but also in other, non-inhibitory forms including cleaved and/or degraded. To test a hypothesis that AAT dependent on its molecular form may have multiple effects on tumour cell behaviour, breast cancer cells, MDA-MB 468, were cultured alone or stimulated with a native AAT or its C-terminal fragment (C-36) at a concentration of 5mumol/l = for 2, 24 and 48 hours. Native AAT... (More)
- The degradation of extracellular matrix during cancer invasion results from the action of several protease and protease inhibitor systems. alpha(1)-Antitrypsin (AAT) is a serine proteinase inhibitor produced by various tumour cells, and its plasma concentration rises during inflammation, infection and malignant diseases. AAT is found in a native, inhibitory active form, but also in other, non-inhibitory forms including cleaved and/or degraded. To test a hypothesis that AAT dependent on its molecular form may have multiple effects on tumour cell behaviour, breast cancer cells, MDA-MB 468, were cultured alone or stimulated with a native AAT or its C-terminal fragment (C-36) at a concentration of 5mumol/l = for 2, 24 and 48 hours. Native AAT added to the cells for 2 hours enhanced transforming growth factor beta 1 (TGFbeta1) levels by 50%, but inhibited cell proliferation (by 61%), reduced interleukin 6 (IL-6) levels (by 87%) and activity (by about 66%), compared with non-stimulated cells. Native AAT showed similar, but less pronounced, effects when added to the cells for 24 and 48 hours. Under the same experimental conditions the cells exposed to the C-36 peptide significantly increased in proliferation, invasiveness and showed higher IL-6 levels. In addition, cells treated with the C-36 for 48 hours increased in NFkappaB (nuclear factor kappa B) activity. These results indicate that AAT, dependent on its molecular form, can both suppress and induce breast tumour cell biological activity in vitro. (C) 2003 Lippincott Williams Wilkins. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/900440
- author
- Zelvyté, Inga LU ; Lindgren, Stefan LU and Janciauskiene, Sabina LU
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- serpins, proteinases, alpha(1)-antitrypsin, C-terminal fragment of, breast tumour cells
- in
- European Journal of Cancer Prevention
- volume
- 12
- issue
- 2
- pages
- 117 - 124
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000182792500005
- pmid:12671535
- ISSN
- 1473-5709
- DOI
- 10.1097/01.cej.0000062793.86004.20
- language
- English
- LU publication?
- yes
- id
- fbb9d689-6705-4431-a45e-5ed7ea7d10a7 (old id 900440)
- alternative location
- http://www.eurjcancerprev.com/pt/re/ejcp/abstract.00008469-200304000-00005.htm
- date added to LUP
- 2016-04-01 12:30:58
- date last changed
- 2018-11-21 20:08:13
@article{fbb9d689-6705-4431-a45e-5ed7ea7d10a7,
abstract = {{The degradation of extracellular matrix during cancer invasion results from the action of several protease and protease inhibitor systems. alpha(1)-Antitrypsin (AAT) is a serine proteinase inhibitor produced by various tumour cells, and its plasma concentration rises during inflammation, infection and malignant diseases. AAT is found in a native, inhibitory active form, but also in other, non-inhibitory forms including cleaved and/or degraded. To test a hypothesis that AAT dependent on its molecular form may have multiple effects on tumour cell behaviour, breast cancer cells, MDA-MB 468, were cultured alone or stimulated with a native AAT or its C-terminal fragment (C-36) at a concentration of 5mumol/l = for 2, 24 and 48 hours. Native AAT added to the cells for 2 hours enhanced transforming growth factor beta 1 (TGFbeta1) levels by 50%, but inhibited cell proliferation (by 61%), reduced interleukin 6 (IL-6) levels (by 87%) and activity (by about 66%), compared with non-stimulated cells. Native AAT showed similar, but less pronounced, effects when added to the cells for 24 and 48 hours. Under the same experimental conditions the cells exposed to the C-36 peptide significantly increased in proliferation, invasiveness and showed higher IL-6 levels. In addition, cells treated with the C-36 for 48 hours increased in NFkappaB (nuclear factor kappa B) activity. These results indicate that AAT, dependent on its molecular form, can both suppress and induce breast tumour cell biological activity in vitro. (C) 2003 Lippincott Williams Wilkins.}},
author = {{Zelvyté, Inga and Lindgren, Stefan and Janciauskiene, Sabina}},
issn = {{1473-5709}},
keywords = {{serpins; proteinases; alpha(1)-antitrypsin; C-terminal fragment of; breast tumour cells}},
language = {{eng}},
number = {{2}},
pages = {{117--124}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{European Journal of Cancer Prevention}},
title = {{Multiple effects of alpha(1)-antitrypsin on breast carcinoma MDA-MB 468 cell growth and invasiveness}},
url = {{http://dx.doi.org/10.1097/01.cej.0000062793.86004.20}},
doi = {{10.1097/01.cej.0000062793.86004.20}},
volume = {{12}},
year = {{2003}},
}