The role of hyaluronic acid interacting molecule neurocan in pancreatic cancer and peritoneal metastasis

Xu, Yali 2025. The role of hyaluronic acid interacting molecule neurocan in pancreatic cancer and peritoneal metastasis. PhD Thesis, Cardiff University. Item availability restricted.

	PDF (Cardiff University Electronic Publication Form) - Supplemental Material Restricted to Repository staff only Download (209kB)
	PDF - Accepted Post-Print Version Restricted to Repository staff only until 13 April 2027 due to copyright restrictions. Download (19MB)

Abstract

Neurocan (NCAN) is a secreted proteoglycan mainly expressed in the central nervous system, where it is known to regulate neuronal generation. Its function in cancer is highly context-dependent, promoting malignancy in brain tumours but correlating with improved survival in Merkel cell carcinoma. This study aimed to elucidate the biological functions of NCAN in pancreatic cancer and its contribution to peritoneal dissemination Clinically, NCAN expression was downregulated in primary pancreatic tumours, correlating with poorer overall and relapse-free survival. Conversely, NCAN expression was elevated in distant metastases compared to primary tumours, suggesting a dual role in tumour progression. This indicates that NCAN may play different roles during the disease progression. To investigate its function, we modulated NCAN levels in pancreatic cell lines. The in vitro experiments showed that while NCAN promoted several malignant traits, including cancer cell proliferation, clonogenic growth, and migration, it paradoxically acted as a potent invasion suppressor. Overexpression of NCAN significantly impaired the cancer cells’ ability to invade through Matrigel and mesothelial cell monolayers, whereas knocking down NCAN enhanced their invasiveness. Mechanistically, NCAN overexpression inhibited invasion by downregulating the expression of matrix metalloproteinases MMP1 and MMP3, thus hindering extracellular matrix degradation. The study also noted that factors secreted by peritoneal mesothelial cells, as well as hyaluronic acid, could independently inhibit cancer cell invasion. In conclusion, loss of NCAN in primary pancreatic tumour was associated with worse patient survival. The study functionally establishes NCAN as a key invasion suppressor that operates by regulating MMPs. These findings highlight a protective role for NCAN against tumour progression, warranting further investigation into its precise molecular pathways and the therapeutic potential of targeting the NCAN-MMP axis in pancreatic cancer.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Engineering
Uncontrolled Keywords:	1. Pancreatic cancer 2. Peritoneal dissemination 3. Cancer cell invasion 4. Neurocan (NCAN) 5. Hyaluronic acid interacting molecules 6. Pulsed electromagnetic field exposure (PEFE)
Date of First Compliant Deposit:	13 April 2026
Last Modified:	17 Apr 2026 09:51
URI:	https://orca.cardiff.ac.uk/id/eprint/186307

Actions (repository staff only)

Edit Item