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A study of the desmoplastic reaction in pancreatic cancer and its effect on malignant phenotype

A study of the desmoplastic reaction in pancreatic cancer and its effect on malignant phenotype
A study of the desmoplastic reaction in pancreatic cancer and its effect on malignant phenotype

Pancreatic cancer (PC) is characterised by a profound desmoplastic reaction, which contains fibrillar collagen (collagen type I and III).

Histological examination of PCs using immunohistochemistry demonstrated gross distortion of structure of the normal pancreas. The glandular structures of the normal pancrease (surrounding by type IV collagen) were altered in PC, with wide bands of fibrotic stroma (containing type I collagen) separating the malignant glands. Numerous myofibroblastic pancreatic stellate cells (PSC) were identified throughout the desmoplastic reaction, often closely associated with cancer cells.

Potential interaction between PSC and cancer cells were tested in vitro using primary cultures of human PSC and pancreatic cancer cell lines (MIA PaCa-2, Panc-1 and AsPC-1). Conditioned media from each PC cell line stimulated proliferation of PSC. PSC secreted collagen in excess of the cancer cells. Furthermore conditioned media from AsPC-1 cells increased PSC procollagen 1 gene expression and collagen secretion (which correlated with TGFβ1 expression).  PSC expressed tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) at high levels (compared to matrix metalloprotease-2) thus promoting the accumulation of extracellular matrix.

There is a detrimental interaction between pancreatic cancer cells and PSC that stimulates formation of the desmoplastic reaction abundant in type I collagen. In turn, type I collagen promotes growth of malignant cells in pancreatic cancer. This contributes to the understanding of the origin of the desmoplastic reaction by defining the interaction between pancreatic cancer cells and primary cultures of human PSC. Moreover, it demonstrates that the consequence of these interactions is deleterious to the host.

University of Southampton
Armstrong, Thomas
3b87df01-cd08-4048-91c4-7390c73a5960
Armstrong, Thomas
3b87df01-cd08-4048-91c4-7390c73a5960

Armstrong, Thomas (2003) A study of the desmoplastic reaction in pancreatic cancer and its effect on malignant phenotype. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Pancreatic cancer (PC) is characterised by a profound desmoplastic reaction, which contains fibrillar collagen (collagen type I and III).

Histological examination of PCs using immunohistochemistry demonstrated gross distortion of structure of the normal pancreas. The glandular structures of the normal pancrease (surrounding by type IV collagen) were altered in PC, with wide bands of fibrotic stroma (containing type I collagen) separating the malignant glands. Numerous myofibroblastic pancreatic stellate cells (PSC) were identified throughout the desmoplastic reaction, often closely associated with cancer cells.

Potential interaction between PSC and cancer cells were tested in vitro using primary cultures of human PSC and pancreatic cancer cell lines (MIA PaCa-2, Panc-1 and AsPC-1). Conditioned media from each PC cell line stimulated proliferation of PSC. PSC secreted collagen in excess of the cancer cells. Furthermore conditioned media from AsPC-1 cells increased PSC procollagen 1 gene expression and collagen secretion (which correlated with TGFβ1 expression).  PSC expressed tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) at high levels (compared to matrix metalloprotease-2) thus promoting the accumulation of extracellular matrix.

There is a detrimental interaction between pancreatic cancer cells and PSC that stimulates formation of the desmoplastic reaction abundant in type I collagen. In turn, type I collagen promotes growth of malignant cells in pancreatic cancer. This contributes to the understanding of the origin of the desmoplastic reaction by defining the interaction between pancreatic cancer cells and primary cultures of human PSC. Moreover, it demonstrates that the consequence of these interactions is deleterious to the host.

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Published date: 2003

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Local EPrints ID: 465426
URI: http://eprints.soton.ac.uk/id/eprint/465426
PURE UUID: ed21188e-7385-4442-aa7c-06ac5af64d47

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Date deposited: 05 Jul 2022 00:55
Last modified: 23 Jul 2022 02:15

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Author: Thomas Armstrong

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