Implication of capillary morphogenesis gene 2 (CMG2)in the disease progression and peritoneal metastasis of pancreatic cancer

Fang, Ziqian 2023. Implication of capillary morphogenesis gene 2 (CMG2)in the disease progression and peritoneal metastasis of pancreatic cancer. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

CMG2 (Capillary morphogenesis gene 2) has been implicated in certain cancers and tumour-associated angiogenesis. CMG2 acts as a tumour suppressor in endocrinerelated cancers such as prostate cancer and breast cancer. In contrast, CMG2 can promote disease progression and distant metastasis in glioma and gastric cancer. The present study aimed to dissect the role of CMG2 in pancreatic cancer and diseasespecific peritoneal metastasis. CMG2 was found to be upregulated in pancreatic cancer tissues and associated with a poor prognosis. CMG2 was increased in metastatic lesions and those primary tumours which had distant metastases at the diagnosis of the disease. This suggests that CMG2 may promote the distant metastasis of pancreatic cancer. The influence of CMG2 on cellular functions was determined in pancreatic cancer cell lines, with CMG2 overexpression or knockdown. CMG2 promoted cell-matrix adhesion in PANC-1 and ASPC-1 cells, suggesting CMG2 can enhance cell-matrix adhesion. CMG2 enhanced cell aggregation of MiaPaCa-2 cells. CMG2 also facilitated adhesion of PANC-1 cells to mesothelial cells. CMG2-promoted adhesion of PANC-1 cells to mesothelial cells was partially blocked after treatment with soluble hyaluronic acid (HA). Furthermore, CMG2 promoted survival of disseminating pancreatic cancer cells, leading to evasion of anoikis. Proteomics analysis showed that the EGFR and focal adhesion pathways were activated in pancreatic cancer cells, with overexpression of CMG2. ICAM-1, VCAN and CD44 expression were also increased in pancreatic cancer cells with higher CMG2, which may be involved in CMG2 promoted cell-cell aggregation and cell-HA interaction. In conclusion, CMG2 was upregulated in pancreatic cancer, which was associated with poor prognosis and distant metastasis. CMG2 promoted cell-matrix adhesion, cell-cell adhesion, cell HA interaction, viability and survival of suspended pancreatic cancer cells, may facilitate the dissemination of pancreatic cancer cells to the peritoneum, in which enhanced EGFR and FAK pathways were likely involved. Furthermore, the expression of integrins, tight junction proteins and HA interacting molecules were also enhanced by CMG2. Further study will shed light on the exact molecular mechanisms and therapeutic potential of targeting CMG2 in pancreatic cancer.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	8 December 2023
Last Modified:	08 Dec 2023 14:36
URI:	https://orca.cardiff.ac.uk/id/eprint/164631

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