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Tumour-derived TGF-?1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells

Tumour-derived TGF-?1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells
Tumour-derived TGF-?1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells
The development of an altered stromal microenvironment is a common feature of many tumours including squamous cell carcinoma (SCC), and there is increasing evidence that these changes in the stroma, which include increased expression of proteases and cytokines, may actually promote tumour progression. A common finding is that stromal fibroblasts become ‘activated’ myofibroblasts, expressing smooth muscle actin and secreting cytokines, proteases and matrix proteins. We show that myofibroblasts are commonly found in the stroma of oral SCC and are often concentrated at the invasive margin of the tumour. Using oral SCC cells and primary oral fibroblasts, we demonstrate that tumour cells directly induce a myofibroblastic phenotype, and that this transdifferentiation is dependent on SCC-derived TGF-?1. In turn, myofibroblasts secrete significantly higher levels of hepatocyte growth factor/scatter factor compared with fibroblast controls, and this cytokine promotes SCC invasion through Matrigel, a mixture of basement membrane proteins. This is the first time that this double paracrine mechanism has been demonstrated between squamous carcinoma cells and fibroblasts, and emphasises that cancer invasion can be promoted indirectly by the release of tumour-induced host factors from stroma.
squamous carcinoma, TGF-?1, invasion, scatter factor, hepatocyte growth factor, myofibroblast, stroma
0007-0920
822-832
Lewis, M.P.
fc7ecc9e-98b3-4770-8b40-188a665b5976
Lygoe, K.A.
bf84707f-4c6e-46c8-8e15-cc0310eb6d78
Nystrom, M.L.
94075a8e-33fa-416d-8376-92409c880f89
Anderson, W.P.
57c10723-6a29-4aa4-b19f-13161750eede
Speight, P.M.
e5e8d0a3-c9d8-4054-aa9e-c6a186c48e9f
Thomas, G.J.
2ff54aa9-a766-416b-91ee-cf1c5be74106
Lewis, M.P.
fc7ecc9e-98b3-4770-8b40-188a665b5976
Lygoe, K.A.
bf84707f-4c6e-46c8-8e15-cc0310eb6d78
Nystrom, M.L.
94075a8e-33fa-416d-8376-92409c880f89
Anderson, W.P.
57c10723-6a29-4aa4-b19f-13161750eede
Speight, P.M.
e5e8d0a3-c9d8-4054-aa9e-c6a186c48e9f
Thomas, G.J.
2ff54aa9-a766-416b-91ee-cf1c5be74106

Lewis, M.P., Lygoe, K.A., Nystrom, M.L., Anderson, W.P., Speight, P.M. and Thomas, G.J. (2004) Tumour-derived TGF-?1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells. British Journal of Cancer, 90 (4), 822-832. (doi:10.1038/sj.bjc.6601611).

Record type: Article

Abstract

The development of an altered stromal microenvironment is a common feature of many tumours including squamous cell carcinoma (SCC), and there is increasing evidence that these changes in the stroma, which include increased expression of proteases and cytokines, may actually promote tumour progression. A common finding is that stromal fibroblasts become ‘activated’ myofibroblasts, expressing smooth muscle actin and secreting cytokines, proteases and matrix proteins. We show that myofibroblasts are commonly found in the stroma of oral SCC and are often concentrated at the invasive margin of the tumour. Using oral SCC cells and primary oral fibroblasts, we demonstrate that tumour cells directly induce a myofibroblastic phenotype, and that this transdifferentiation is dependent on SCC-derived TGF-?1. In turn, myofibroblasts secrete significantly higher levels of hepatocyte growth factor/scatter factor compared with fibroblast controls, and this cytokine promotes SCC invasion through Matrigel, a mixture of basement membrane proteins. This is the first time that this double paracrine mechanism has been demonstrated between squamous carcinoma cells and fibroblasts, and emphasises that cancer invasion can be promoted indirectly by the release of tumour-induced host factors from stroma.

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Published date: 17 February 2004
Keywords: squamous carcinoma, TGF-?1, invasion, scatter factor, hepatocyte growth factor, myofibroblast, stroma

Identifiers

Local EPrints ID: 66691
URI: http://eprints.soton.ac.uk/id/eprint/66691
ISSN: 0007-0920
PURE UUID: e5496294-a4bb-48aa-925e-995ba9049530

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Date deposited: 10 Jul 2009
Last modified: 13 Mar 2024 18:30

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Contributors

Author: M.P. Lewis
Author: K.A. Lygoe
Author: M.L. Nystrom
Author: W.P. Anderson
Author: P.M. Speight
Author: G.J. Thomas

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