Mesenchymal Stem Cells and Sarcoma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F24%3A10490977" target="_blank" >RIV/00216208:11140/24:10490977 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1016/B978-0-443-15717-2.00116-5" target="_blank" >https://doi.org/10.1016/B978-0-443-15717-2.00116-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/B978-0-443-15717-2.00116-5" target="_blank" >10.1016/B978-0-443-15717-2.00116-5</a>

Result language

angličtina

Original language name

Mesenchymal Stem Cells and Sarcoma

Original language description

Sarcomas encompass a wide range of mesenchymal tumors, most of them manifesting a partial mesenchymal differentiation, which is the cornerstone of their basic pathological classification. A family of related stem cell types, including, first and foremost, the mesenchymal stem cells, and also neural crest-derived stem cells and skeletal muscle satellite cells, are regarded as probable candidates for sarcoma cells-of-origin. Sarcoma development usually features limited parallels to normal mesenchymal differentiation pathways, with a specific terminal differentiation block resulting in an inability to acquire a mature phenotype. Accordingly, many of the regulatory proteins implicated in the normal mesenchymal stem cell differentiation are also involved in sarcomagenesis, either as inducers of the limited mesenchymal differentiation specifying a particular sarcoma type, or as targets of sarcoma-specific oncogenes precluding the terminal differentiation (or both); the Runx2-overexpressing osteosarcomas, the Sox9-overexpressing chondrosarcomas and, in a certain sense, also the myocardin-overexpressing leiomyosarcomas can be cited as typical examples. The issue of the mesenchymal (and by extension also sarcomatoid) differentiation is additionally complicated by the fact that most of the regulatory factors actually exert a dual function, promoting stemness and at the same time a particular differentiation pathway, and their impact on sarcoma development will be crucially dependent on the particular signaling context; indeed, both the mesenchymal differentiation and sarcomagenesis include a complex signaling interplay and networking. The signals impinging on both the mesenchymal differentiation and sarcoma development are thus to be understood in a broad sense, involving not only soluble hormonal or pharmaceutical signals, but also microenvironmental cues and mechanosignals; many of these divergent signals are integrated by the Hippo-YAP signaling pathway. Exclusive to sarcomagenesis are intrinsic inputs resulting from accumulated oncogenic mutations and epigenetic modifications. These can either be very copious and dynamic, as is typical for adult sarcomas, or very specific and focused, as usual in mostly pediatric or early adult-onset translocation-dependent sarcomas. The myxoid liposarcoma is such an example, where the specific fusion oncoprotein brought about by the corresponding reciprocal translocation induces a differentiation arrest just in the middle of the adipogenic differentiation pathway. Not all sarcomas show a residual mesenchymal differentiation, the undifferentiated sarcomas may either evade differentiation by simultaneously activating mutually interfering differentiation pathways or by losing all residual differentiation secondarily, during their progression. Ewing sarcoma provides yet another example, where the translocation-born fusion oncoprotein exerts a particularly profound reprogramming effect, which also precludes any mesenchymal differentiation. Neural crest-derived stem cells complement mesenchymal stem cells in many traditional locations, but they dominate stem cell pools in some anatomical regions, like the orofacial region, to become cells-of-origin for specific sarcoma subtypes, like Kaposi sarcoma. Besides, their differentiation potential seems to be broader than that of the mesoderm-derived mesenchymal stem cells and includes also neuronal and Schwann cell, which is pertinent for another special sarcoma subtype, the malignant peripheral nerve sheath tumor. A particularly complex combination of stem cell types is to be found in the skeletal muscle, where satellite cells closely cooperate with a special population of mesoderm-derived mesenchymal stem cells known as fibro-adipogenic progenitors, and faithful mechanistic parallels could be identified between the normal skeletal muscle differentiation and regeneration on the one hand, and sarcomagenesis on the other. Indeed, both of the skeletal muscle derived sarcoma types, the rhabdomyosarcoma and the undifferentiated pleomorphic sarcoma, seem to hijack crucial stemness and regeneration signaling pathways. Two essential functions can be ascribed to the fibro-adipogenic progenitors in the context of skeletal muscle sarcomagenesis-for some sarcomas, they can become cells-of-origin, for others, they can act as a sort of stromal supportive cells. The latter aspect of mesoderm-derived mesenchymal stem cell function can be identified across various other sarcoma subtypes, and the vascularly located mesenchymal stem cells seem to act in this way in most documented cases.

Czech name

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Czech description

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Type

C - Chapter in a specialist book

CEP classification

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OECD FORD branch

10600 - Biological sciences

Project

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Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Book/collection name

Comprehensive Hematology and Stem Cell Research

ISBN

978-0-443-15717-2

Number of pages of the result

35

Pages from-to

287-321

Number of pages of the book

2592

Publisher name

Elsevier

Place of publication

Amsterdam

UT code for WoS chapter

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