Contraction of collagen gels by intestinal epithelial cells depends on microfilament function

Olson, Allan

doi:10.1007/bf01316489

Cited by 9 publications

(6 citation statements)

References 27 publications

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“…Function blocking of α2β1 integrin, but not α1β1 integrin, also inhibited the ability of primary cultures to shrink the collagen gel in which they were embedded, suggesting that α2β1 rather than α1β1 is the main collagen I receptor on the primary cultured cells. Collagen contraction, a property only previously reported for certain cultured intestinal epithelial cell lines , was also unaffected by inhibitors of actin, myosin II or microtubules.…”

Section: Discussionsupporting

confidence: 56%

Cellular polarity modulates drug resistance in primary colorectal cancers via orientation of the multidrug resistance protein ABCB1

Ashley

Ouaret

Bodmer

2019

The Journal of Pathology

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Colonic epithelial cells are highly polarised with a lumen‐facing apical membrane, termed the brush border, and a basal membrane in contact with the underlying extracellular matrix (ECM). This polarity is often maintained in cancer tissue in the form of neoplastic glands and has prognostic value. We compared the cellular polarity of several ex vivo spheroid colonic cancer cultures with their parental tumours and found that those grown as non‐attached colonies exhibited apical brush border proteins on their outer cellular membranes. Transfer of these cultures to an ECM, such as collagen, re‐established the centralised apical polarity observed in vivo . The multidrug resistance protein ABCB1 also became aberrantly polarised to outer colony membranes in suspension cultures, unlike cultures grown in collagen, where it was polarised to central lumens. This polarity switch was dependent on the presence of serum or selected serum components, including epidermal growth factor (EGF), transforming growth factor‐β1 (TGF‐β1) and insulin‐like growth factor‐1 (IGF‐1). The apical/basal orientation of primary cancer colon cultures cultured in collagen/serum was modulated by α2β1 integrin signalling. The polarisation of ABCB1 in colonies significantly altered drug uptake and sensitivity, as the outward polarisation of ABCB1 in suspension colonies effluxed substrates more effectively than ECM‐grown colonies with ABCB1 polarised to central lumens. Thus, serum‐free suspension colonies were more resistant to a variety of anti‐cancer drugs than ECM‐grown colonies. In conclusion, the local stroma, or absence thereof, can have profound effects on the sensitivity of colorectal cultures to drugs that are ABCB1 substrates. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Section: Discussionsupporting

confidence: 56%

Cellular polarity modulates drug resistance in primary colorectal cancers via orientation of the multidrug resistance protein ABCB1

Ashley

Ouaret

Bodmer

2019

The Journal of Pathology

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“…29,37 However, long-term culture of cells on a soft material such as collagen (112 ± 37 Pa, n = 3) leads to collagen contraction due to mechanical forces imparted by the cells. 38 Thus, microstructures fabricated from unmodified collagen are not suitable as a cell scaffold because of collagen deformation over time. For this reason, we also cultured crypts on a stiffer collagen surface, a cross-linked collagen hydrogel (8640 ± 77 Pa, n = 3).…”

Section: Resultsmentioning

confidence: 99%

In Vitro Generation of Mouse Colon Crypts

Wang

Gunasekara

Attayek

et al. 2017

ACS Biomater. Sci. Eng.

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Organoid culture has had a significant impact on in vitro studies of the intestinal epithelium; however, the exquisite architecture, luminal accessibility, and lineage compartmentalization found in vivo has not been recapitulated in the organoid systems. We have used a microengineered platform with suitable extracellular matrix contacts and stiffness to generate a self-renewing mouse colonic epithelium that replicates key architectural and physiological functions found in vivo, including a surface lined with polarized crypts. Chemical gradients applied to the basal–luminal axis compartmentalized the stem/progenitor cells and promoted appropriate lineage differentiation along the in vitro crypt axis so that the tissue possessed a crypt stem cell niche as well as a layer of differentiated cells covering the luminal surface. This new approach combining microengineered scaffolds, native chemical gradients, and biophysical cues to control primary epithelium ex vivo can serve as a highly functional and physiologically relevant in vitro tissue model.

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“…The presence of this layer is essential, since its removal by forceps or mucolytic agents impairs restitution [12]. Another factor that appears to assist the process is the reduction of the area required for resurfacing, mediated by contraction of subepithelial myofibroblasts [13] and possibly by tractional forces generated by the epithelial cells themselves [14].…”

Section: Restitutionmentioning

confidence: 99%

Epithelial Migration in the Colon: Filling in the Gaps

Wilson

Gibson

1997

Clinical Science

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1. The efficient repair of gastrointestinal mucosal injuries is essential in the preservation of the epithelial barrier to luminal antigens. Accumulated evidence suggests that epithelial migration plays a major part in this repair by rapidly resealing defects induced by both physiological and pathological insults, a process termed restitution. 2. This migration has been modelled in various ways, most commonly in mechanically wounded monolayers of cell lines or cells in primary culture, and in wounded human or animal tissue. Evidence from these models indicates that migration is a highly complex process, which is likely to involve the tightly controlled spatial and temporal interaction of multiple factors: (i) extracellular molecules such as soluble factors (e.g. growth factors, trefoil peptides, cytokines) and matrix components (e.g. collagen, laminin, fibronectin); (ii) signalling molecules activated by the interaction of these factors with cell surface receptors (e.g. protein kinases, phospholipases, low-molecular-weight GTPases); (iii) factors which regulate adhesion to other cells (e.g. E-cadherin) and to matrix components (e.g. integrins, hyaluronic acid receptors); (iv) factors which regulate detachment from the extracellular matrix (e.g. urokinase-type plasminogen activator, matrix metalloproteinases); and (v) molecules which regulate cytoskeletal function (e.g. Rac), which allows the formation of specialized cellular processes termed lamellipodia. 3. The identification of physiologically relevant factors that stimulate epithelial cell migration, and a better understanding of their mechanism of action, may be beneficial in the development of novel therapeutic approaches in diseases such as inflammatory bowel disease through the pharmacological or dietary enhancement of this migration.

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Contraction of collagen gels by intestinal epithelial cells depends on microfilament function

Cited by 9 publications

References 27 publications

Cellular polarity modulates drug resistance in primary colorectal cancers via orientation of the multidrug resistance protein ABCB1

Cellular polarity modulates drug resistance in primary colorectal cancers via orientation of the multidrug resistance protein ABCB1

In Vitro Generation of Mouse Colon Crypts

Epithelial Migration in the Colon: Filling in the Gaps

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