Psoriasin promotes invasion, aggregation and survival of pancreatic cancer cells; association with disease progression

Liu, Ying, Bunston, Carly, Hodson, Nicholas, Resaul, Jeyna, Sun, Ping-Hui, Cai, Shuo, Chen, Gang, Gu, Yanan, Satherley, Lucy, Bosanquet, David C. ORCID: https://orcid.org/0000-0003-2304-0489, Al-Sarireh, Bilal, Tian, Xiuyun, Hao, Chunyi, Jiang, Wen ORCID: https://orcid.org/0000-0002-3283-1111 and Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409 2017. Psoriasin promotes invasion, aggregation and survival of pancreatic cancer cells; association with disease progression. International Journal of Oncology 50 (5) , pp. 1491-1500. 10.3892/ijo.2017.3953

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Abstract

Psoriasin (S100A7) is an 11-kDa small calcium binding protein initially isolated from psoriatic skin lesions. It belongs to the S100 family of proteins which play an important role in a range of cell functions including proliferation, differentiation, migration and apoptosis. Aberrant Psoriasin expression has been implicated in a range of cancers and is often associated with poor prognosis. This study examined the role of Psoriasin on pancreatic cancer cell functions and the implication in progression of the disease. Expression of Psoriasin was determined in a cohort of pancreatic tissues comprised of 126 pancreatic tumours and 114 adjacent non-tumour pancreatic tissues. Knockdown and overexpression of Psoriasin in pancreatic cancer cells was performed using specifically constructed plasmids, which either had anti-Psoriasin ribozyme transgene or the full length human Psoriasin coding sequence. Psoriasin knockdown and overexpression was verified using conventional RT-PCR and qPCR. The effect of manipulating Psoriasin expression on pancreatic cancer cell functions was assessed using several in vitro cell function assays. Local invasive pancreatic cancers extended beyond the pancreas expressed higher levels of Psoriasin transcripts compared with the cancers confined to the pancreas. Primary tumours with distant metastases exhibited a reduced expression of Psoriasin. Psoriasin overexpression cell lines exhibited significantly increased growth and migration compared to control cells. In addition, Psoriasin overexpression resulted in increased pancreatic cancer cell invasion which was associated with upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Overexpression of Psoriasin also promoted aggregation and survival of pancreatic cancer cells when they lost anchorage. Taken together, higher expression of Psoriasin was associated with local invasion in pancreatic cancers. Psoriasin expression is associated with pancreatic cancer cell growth, migration, cell-matrix adhesion, and invasion via regulation of MMPs. As such, the proposed implications of Psoriasin in invasion, disease progression and as a potential therapeutic target warrant further investigation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Psoriasin, S100A7, pancreatic cancer, adhesion, invasion, metastasis
Publisher:	Spandidos Publications
ISSN:	1019-6439
Funders:	Cancer Research Wales, Life Sciences Research Network Wales (Welsh Government's Ser Cymru Program) and Albert huang Foundation, China Medical Scholarship from the Cardiff University.
Date of First Compliant Deposit:	10 April 2017
Date of Acceptance:	28 February 2017
Last Modified:	21 Jun 2024 01:10
URI:	https://orca.cardiff.ac.uk/id/eprint/99785

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