The stroma reaction myofibroblast:  a key player in the control of tumor cell behavior

Desmoulière, Alexis; Guyot, Christelle; Gabbiani, Giulio

doi:10.1387/ijdb.041802ad

Cited by 508 publications

(492 citation statements)

References 82 publications

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“…22 In contrast to hepatocytes that occupy almost 80% of the total liver volume and perform the majority of numerous liver functions, nonparenchymal liver cells, which contribute only 6.5% to the liver volume, but 40% to the total number of liver cells, are localized in the sinusoidal compartment of the tissue. [24][25][26] Although hepatocytes comprise almost 80% of the liver, there are at least another ten cell types, many of which provide ''cross-talk'' and play important functional roles in the normal and diseased liver. 25,26 It has been increasingly recognized that both under normal and pathological conditions, many hepatocyte functions are regulated by substances released from neighboring non-parenchymal cells.…”

Section: The Livermentioning

confidence: 99%

“…[24][25][26] Although hepatocytes comprise almost 80% of the liver, there are at least another ten cell types, many of which provide ''cross-talk'' and play important functional roles in the normal and diseased liver. 25,26 It has been increasingly recognized that both under normal and pathological conditions, many hepatocyte functions are regulated by substances released from neighboring non-parenchymal cells. 24,27 Liver sinusoidal endothelial cells constitute the lining or wall of the hepatic sinusoid.…”

Section: The Livermentioning

confidence: 99%

“…They are also active in the secretion of cytokines, eicosanoids (i.e., prostanoids and leukotrienes), endothelin-1, nitric oxide, and some ECM components. 24,26 Kupffer cells are intrasinusoidal macrophages with a pronounced endocytic and phagocytic capability. They are in constant contact with gut-derived particulate materials and soluble bacterial products so that a sub-threshold level of their activation in the normal liver may be anticipated.…”

Section: The Livermentioning

confidence: 99%

“…Moreover, during liver injury and inflammation, Kupffer cells secrete enzymes and cytokines that may damage hepatocytes, and are active in the remodeling of ECM. 24,26 Hepatic stellate cells are present in the perisinusoidal space. They are characterized by abundance of intracytoplasmic fat droplets and the presence of well-branched cytoplasmic processes, which embrace endothelial cells and provide focally a double lining for sinusoid.…”

Section: The Livermentioning

confidence: 99%

“…Acute damage to hepatocytes activates transformation of quiescent stellate cells into myofibroblast-like cells that play a key role in the development of inflammatory fibrotic response. 24,26 Pit cells represent a liver-associated population of large granular lymphocytes, i.e., NK cells, which fulfill functions in pathogen defense, T-cell recruitment, and modulation of liver injury. 24 They spontaneously kill a variety of tumor cells in an MHC-unrestricted way, and this anti-tumor activity may be enhanced by the secretion of interferon-g.…”

Section: The Livermentioning

confidence: 99%

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Pluripotent plasticity of stem cells and liver repopulation

Gennero

Roos

Sperber

et al. 2010

Cell Biochemistry & Function

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Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra-hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self-repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio-artificial liver-assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver.

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Section: The Livermentioning

confidence: 99%

Section: The Livermentioning

confidence: 99%

Section: The Livermentioning

confidence: 99%

Section: The Livermentioning

confidence: 99%

Section: The Livermentioning

confidence: 99%

See 3 more Smart Citations

Pluripotent plasticity of stem cells and liver repopulation

Gennero

Roos

Sperber

et al. 2010

Cell Biochemistry & Function

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Adipose‐derived mesenchymal stem cells differentiate into pancreatic cancer‐associated fibroblasts in vitro

et al. 2020

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Cancer-associated fibroblasts (CAFs) are key components of the dense, proliferating stroma observed in pancreatic ductal adenocarcinoma (PDAC), and CAF subpopulations drive tumor heterogeneity and play a major role in PDAC progression and drug resistance. CAFs consist of heterogenous subpopulations such as myoblastic CAF (myCAF) and inflammatory CAF (iCAF), and each has distinct essential roles. However, it is not clear how CAF subpopulations are formed in PDAC. Adiposederived MSCs (AD-MSCs), which possess a high multilineage potential and self-renewal capacity, are reported to be one of the in vivo CAF sources. Here, we aimed to investigate whether AD-MSCs can act as precursors for CAFs in vitro. We recorded morphological features and collected omics data from two in vitro co-culture models for recapitulating clinical PDAC. Additionally, we tested the advantages of the co-culture model in terms of accurately modeling morphology and CAF heterogeneity. We showed that AD-MSCs differentiate into two distinct CAF subpopulations: Direct contact co-culture with PDAC cell line Capan-1 induced differentiation into myCAFs and iCAFs, while indirect co-culture induced differentiation into only iCAFs. Using these co-culture systems, we also identified novel CAF markers that may be helpful for elucidating the mechanisms of CAFs in the tumor microenvironment (TME). In conclusion, AD-MSCs can differentiate into distinct CAF subtypes depending on the different co-culture conditions in vitro, and the identification of potential CAF markers may aid in future investigations of the mechanisms underlying the role of CAFs in the TME.

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The Biology of Tumour Stroma

Guyot¹,

Lepreux

Darby

et al. 2007

The Cancer Handbook

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The cooperation between epithelial and mesenchymal cells is essential for embryonic development and certainly plays an important role in pathological phenomena such as wound healing and tumour progression. Many epithelial tumours are characterised by the local accumulation of connective tissue cells and extracellular material; this phenomenon has been called stroma reaction , which shows many similarities in its organisation and evolution with the granulation tissue that develops during tissue repair. One of the cellular components of stroma reaction is the myofibroblast, a modified fibroblast that has become capable of expression of α‐smooth muscle actin, the actin isoform typical of vascular smooth muscle cells, and also capable of synthesis of significant amounts of collagen and other extracellular matrix components. The myofibroblast is a key cell for connective tissue remodelling that takes place during wound healing and fibrosis development. Myofibroblasts are also capable of interaction with epithelial cells and other connective tissue cells and may thus control such phenomena as tumour invasion and angiogenesis. In this chapter, we discuss the mechanisms of myofibroblast evolution during normal and malignant conditions, and the interaction of myofibroblasts with other cells in order to control tumour progression. On this basis, we suggest that the myofibroblast may represent a new and important target for anti‐tumour therapy.

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The stroma reaction myofibroblast: a key player in the control of tumor cell behavior

Cited by 508 publications

References 82 publications

Pluripotent plasticity of stem cells and liver repopulation

Pluripotent plasticity of stem cells and liver repopulation

Adipose‐derived mesenchymal stem cells differentiate into pancreatic cancer‐associated fibroblasts in vitro

The Biology of Tumour Stroma

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