Role of tissue stroma in cancer cell invasion

De Wever, Olivier; Mareel, Marc

doi:10.1002/path.1398

Cited by 1,042TGF-β signaling in diseasesCancer Cells and MetastasisProtease and Inhibitor Mechanisms

Role of tissue stroma in cancer cell invasion

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De Wever, Olivier, Mareel, Marc·2003·The Journal of Pathology

DOI 10.1002/path.1398

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Abstract

Maintenance of epithelial tissues needs the stroma. When the epithelium changes, the stroma inevitably follows. In cancer, changes in the stroma drive invasion and metastasis, the hallmarks of malignancy. Stromal changes at the invasion front include the appearance of myofibroblasts, cells sharing characteristics with fibroblasts and smooth muscle cells. The main precursors of myofibroblasts are fibroblasts. The transdifferentiation of fibroblasts into myofibroblasts is modulated by cancer cell‐derived cytokines, such as transforming growth factor‐β (TGF‐β). TGF‐β causes cancer progression through paracrine and autocrine effects. Paracrine effects of TGF‐β implicate stimulation of angiogenesis, escape from immunosurveillance and recruitment of myofibroblasts. Autocrine effects of TGF‐β in cancer cells with a functional TGF‐β receptor complex may be caused by a convergence between TGF‐β signalling and β‐catenin or activating Ras mutations. Experimental and clinical observations indicate that myofibroblasts produce pro‐invasive signals. Such signals may also be implicated in cancer pain. N‐Cadherin and its soluble form act as invasion‐promoters. N‐Cadherin is expressed in invasive cancer cells and in host cells such as myofibroblasts, neurons, smooth muscle cells, and endothelial cells. N‐Cadherin‐dependent heterotypic contacts may promote matrix invasion, perineural invasion, muscular invasion, and transendothelial migration; the extracellular, the juxtamembrane and the β‐catenin binding domain of N‐cadherin are implicated in positive invasion signalling pathways. A better understanding of stromal contributions to cancer progression will likely increase our awareness of the importance of the combinatorial signals that support and promote growth, dedifferentiation, invasion, and ectopic survival and eventually result in the identification of new therapeutics targeting the stroma. Copyright © 2003 John Wiley & Sons, Ltd.

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In direct co-culture, physical contact between cells allows for the study of adhesion molecules such as N-cadherins.
“In the former, due to the physical contact between cells, this allows for the study of adhesion molecules such as Ncadherins [50].”
From Microfluidic modelling of the tumor microenvironment for anti-cancer drug development (2019) · cites this paper as [50]
The sections “The normal epithelial ecosystem” and “The cancer ecosystem” describe co-culture systems and direct cell–cell contacts. “Molecular mechanisms of N-cadherin-mediated invasion and migration” links N-cadherin to cell–cell contact, but the paper does not say that direct co-culture is used to study adhesion molecules such as N-cadherin. (LLM, conf=0.83)
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Authors: De Wever, O., & Mareel, M.
Affiliations: Ghent University Hospital (BE)
Corresponding author: Mareel, Marc
Venue: The Journal of Pathology
Publisher: Wiley
Published: 2003-07
Volume: 200
Issue: 4
Pages: 429-447
ISSN: 0022-3417 (ISSN-L)
1096-9896
DOI: 10.1002/path.1398
OpenAlex: W2008714016
Cited by: 1,042
References: 269
Citations by year: 2026: 4 · 2025: 15 · 2024: 24 · 2023: 34 · 2022: 18 · 2021: 38 · 2020: 36 · 2019: 33 · 2018: 41 · 2017: 44 · 2016: 46 · 2015: 55 · 2014: 59 · 2013: 80 · 2012: 82
FWCI: 3.42
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The Journal of Pathology (publishedVersion)
PubMed (publishedVersion)
Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Funders: Kom Op Tegen Kanker, FWO-Vlaanderen, (Brussels
Stichting Emmanuel van der Schueren
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords: tumor stroma, tumor invasion, myofibroblasts, fibroblast transdifferentiation, TGF-beta, TGF-beta signaling, β-catenin, RAS mutations, N-cadherin, perineural invasion, transendothelial migration, cancer pain, metastasis
MeSH terms: Epithelial Cells, Extracellular Matrix, Fibroblasts, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Pain, Signal Transduction, Cadherins, Transforming Growth Factor beta, Stromal Cells, Receptors, Transforming Growth Factor beta, Muscle Cells

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