A1 Refereed original research article in a scientific journal
Keratinocytes and head and neck squamous cell carcinoma cells regulate urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in fibroblasts
Authors: Hakelius M, Koskela A, Ivarsson M, Grenman R, Rubin K, Gerdin B, Nowinski D
Publication year: 2013
Journal: Anticancer Research
Number in series: 8
Volume: 33
Issue: 8
First page : 3113
Last page: 3118
Number of pages: 6
ISSN: 0250-7005
Web address : http://ar.iiarjournals.org/content/33/8/3113.long
BACKGROUND:
To investigate possible differences in the effects of soluble factors from oral squamous cell carcinoma (SCC) cells (UT-SCC-87) and normal oral keratinocytes (NOK) on fibroblast expression of genes involved in tumor stroma turnover.
MATERIALS AND METHODS:
Transwell co-cultures with fibroblasts in collagen gels, and SCC cells or NOK in inserts were carried out. Fibroblast gene expression was measured with real-time polymerase chain reaction (PCR).
RESULTS:
The expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) was up-regulated in co-cultures with SCC cells but not with NOK. In contrast, both SCC cells and NOK regulated matrix metalloproteinase-1 (MMP1) and -3, and tissue inhibitor of metalloproteinases-2 (TIMP2) and -3 to a similar extent, while MMP2 and TIMP1 were largely unaffected. Interleukin 1 alpha (IL1α) up-regulated both MMP1 and MMP3 and down-regulated PAI-1, TIMP2 and -3.
CONCLUSION:
SCC and NOK regulate fibroblast expression of genes involved in tumor stroma turnover differentially in vitro. These observations may contribute to a better understanding of the mechanisms behind extracellular matrix turnover in tumors.
