Contraction of collagen by human fibroblasts and keratinocytes

Souren, J. E. M.; Ponec, Maria; Wijk, Roeland Van

doi:10.1007/bf02624138

Cited by 51 publications

(24 citation statements)

References 19 publications

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“…The ability of normal colon fibroblasts to contract a collagen lattice was markedly enhanced in the presence of colon cancer cells. Interestingly, a reduction of gel size which is greater than the sum of the contraction induced by individual cell types has also been reported recently for co-cultures of human keratinocytes and fibroblasts using visual estimates of gel size (Souren et al, 1989).…”

Section: Discussionsupporting

confidence: 63%

The role of colon fibroblasts in malignant large bowel obstruction – an experimental in vitro model

Agrez

Chua²

1990

Br J Cancer

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SummaryThe mechanism of bowel obstruction in colorectal cancer is likely to involve interactions between tumour cells, host fibroblasts and the extracellular matrix. The role of fibroblast-mediated matrix reorganisation in malignant structures of the large bowel was examined in an in vitro collagen matrix model in which tumour cells and fibroblasts were cultured under serum-free conditions. Colon cancer cells secreted a factor(s) which enhanced the ability of colon fibroblasts to contrast a collagen matrix without an associated mitogenic response by the fibroblasts. Within uncontracted collagen gels marked elongation of fibroblast cell processes was observed in the presence of the tumour-derived factor(s). We propose that matrix reorganisation by host fibroblasts in the wall of the human colon is responsible, at least in part, for malignant large bowel obstruction.Current views indicate that the presence of bowel obstruction adversely influences long-term survival from colorectal cancer and the detrimental effect on prognosis does not appear to be simply a function of more advanced tumour stage (Phillips et al., 1985;Chapuis et al., 1985;Fielding et al., 1986). One possibility is that malignant large bowel obstruction is related to tumour fibrosis since the latter has also been associated with a worse prognosis in rectal cancer (Jass et al., 1986). Although the mechanism of the fibrotic response observed in colorectal cancer remains unclear it is likely to involve not only deposition of new matrix, but also re-organisation of existing stroma.The extracellular matrix is composed largely of collagen, and cell-collagen binding is thought to be mediated by glycoprotein attachment molecules and proteoglycans (Yamada et al., 1985). Human colon carcinomas in organ culture have been found to synthesise proteoglycans and their production in the neoplastic colon appears to be localised to the stromal cell compartment rather than the epithelial compartment lozzo & Wight, 1982). This raises the possibility that colon cancer cells influence binding between host fibroblasts and the surrounding collagen matrix.A characteristic of fibroblasts is their ability to bind strongly to collagen and induce collapse of collagen matrices in vitro. This process is known as collagen lattice contraction, and has been considered analogous to wound contraction in vivo (Bell et al., 1979;Steinberg et al., 1980). Previous work undertaken in our laboratory has shown that human colon cancer cells from established cell lines do not cause significant collagen lattice contraction in vitro in contrast to normal human colon fibroblasts (Agrez, 1989a Fibroblast-mediated contraction of collagen discs Preparation of collagen gels Native type collagen was prepared by acetic acid extraction from rat tail tendons according to the method reported by van Bockxmeer and Martin (1982), and protein concentration estimated (Bio-RAD protein microassay, Bio-RAD Laboratories, CA, USA), according to a modification of the Lowry method (Lowry, et al., 1951). Collagen...

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Section: Discussionsupporting

confidence: 63%

The role of colon fibroblasts in malignant large bowel obstruction – an experimental in vitro model

Agrez

Chua²

1990

Br J Cancer

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“…The spindle-type morphology of the HFs in the HDE gels was consistent with HFs grown in a collagen lattice. 28 Thus, when the HFs were seeded into the three-dimensional collagen lattice they left the mitotic cell cycle and became growth-regulated. This is in agreement with Sarber et 01.…”

Section: Discussionmentioning

confidence: 99%

The generation of a human dermal equivalent to assess the potential contribution of human dermal fibroblasts to the sulphur mustard-induced vesication response

Lindsay

Upshall

1995

Hum Exp Toxicol

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1 A human dermal equivalent (HDE) gel was constructed from rat tail tendon collagen (type 1) and human dermal fibroblasts (HFs). Histological studies revealed that the HFs within the HDE gel matrix assumed the shape of differentiated dermal fibroblasts and were metabolically viable as determined by the MTT assay. 2 The HDE system was developed to determine if viable, differentiated HFs have the potential to contribute to tis sue damage by releasing the proteolytic enzyme elastase following exposure to sulphur mustard (HD). Elastase was measured, using the substrate suc-ala-ala-val-p- nitroanilide (SAAVNA), because of its association with various human pathological bullous skin diseases. An additional elastase substrate (suc-ala-ala-ala-p- nitroanilide ; SAAANA) was also used. A miniaturised assay was employed to measure lactate dehydrogenase (LDH), a cytosolic enzyme released following damage to the cell membrane. 3 Elastase levels (measured with SAAVNA) increased to over 740% of those in control culture medium at 24 h after exposure of the HDE to HD (2 mM) and may there fore be part of the mechanism associated with dermo- epidermal separation and blistering in humans follow ing exposure of skin to HD. LDH was released from the HDE after exposure to HD in a time dependent fashion, suggesting a steady leakage of cytosolic constituents after the initial exposure. 4 The results suggest that differentiated human dermal fibroblasts have the potential to contribute to the devel opment of the vesication response by releasing proteases such as elastase extracellularly after HD exposure. These types of studies cannot be conducted in humans on ethical grounds because of the mutagenic properties of HD. The HDE model therefore has an important advantage in studies on the mechanism of action of HD.

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“…The possible involvement of keratinocytes in wound remodeling was suggested by Souren et al 11 in 1989. These authors reported that collagen gels could be rearranged if keratinocytes were seeded on their surfaces, an effect that was not observed if the cells were seeded inside a gel.…”

Section: Introductionmentioning

confidence: 93%

Role of keratinocytes in wound contraction: an impact assessment using a model of collagen matrix populated with fibroblasts

Isaac

Paggiaro²,

Aldunate³

et al. 2011

Rev. Bras. Cir. Plást. (Impr.)

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ORIGINAL ARtIcLeABSTRACT Background: The possible participation of keratinocytes in wound remodeling has been widely studied. This study investigated the impact of keratinocytes in wound contraction. Methods: Murine type I collagen gels populated by human fibroblasts and seeded with human keratinocytes on the surface to form a dermo-epidermal equivalent were used as the study group. Collagen gels populated by only fibroblasts were used as the control group. The criteria for the preparation and storage of gels were similar for both groups. Results: An evident and statistically significant increase in gel contraction was observed in samples populated by keratinocytes compared to the control group. Conclusions: These results suggest that keratinocytes not only modulate fibroblast proliferation but also play an active role in wound contraction per se. Further research on the mechanisms involved in the communication pathways between cells and between cells and the matrix shall be assessed from the perspective of keratinocyte participation in wound healing and pathologic scarring.

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Contraction of collagen by human fibroblasts and keratinocytes

Cited by 51 publications

References 19 publications

The role of colon fibroblasts in malignant large bowel obstruction – an experimental in vitro model

The role of colon fibroblasts in malignant large bowel obstruction – an experimental in vitro model

The generation of a human dermal equivalent to assess the potential contribution of human dermal fibroblasts to the sulphur mustard-induced vesication response

Role of keratinocytes in wound contraction: an impact assessment using a model of collagen matrix populated with fibroblasts

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