Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth

By M. Quante, S. Tu, H. Tomita, T. Gonda, Sophie S. W. Wang, Shigeo Takashi, G. Baik, W. Shibata, Bethany Diprete, Kelly S. Betz and 4 more. Cancer Cell, 2011

1,006 citations recorded by the source corpus.

Summary Carcinoma associated fibroblasts (CAFs) that express α-smooth-muscle-actin (αSMA) contribute to cancer progression, but their precise origin and role is unclear. Using mouse models of inflammation-induced gastric cancer, we show that at least 20% of CAFs originate from bone marrow (BM) and derive from mesenchymal stem cells (MSCs). αSMA+ myofibroblasts (MF) are niche cells normally present in BM and increase markedly during cancer progression. MSC-derived CAFs that are recruited to the dysplastic stomach express IL-6, Wnt5α and BMP4, show DNA-hypomethylation, and promote tumor growth. Moreover, CAFs are generated from MSCs and are recruited to the tumor in TGF-β- and SDF-1α-dependent manner. Carcinogenesis therefore involves expansion and relocation of BM-niche cells to the tumor to create a niche to sustain cancer progression.

Subfields: Genetics, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/0fcec4bf085ef3ea6f74af9e9d91b98ad9be1068

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In Genetics

1. M. Mareel
2. Natascha Roehlen
3. B. Hinz
4. E. Crouchet
5. T. Baumert
6. R. DePinho
7. O. De Wever
8. T. Stappenbeck

In Oncology

1. B. Hinz
2. M. Mareel
3. O. De Wever
4. Thea D. Tlsty
5. Philippe Gascard
6. R. DePinho
7. G. Karsenty

In Pulmonary and Respiratory Medicine

1. B. Hinz
2. V. Thannickal
3. Nikolaos G. Frangogiannis
4. TA Wynn

Citations in the corpus

• Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth (2015, background): “also showed that at least 20% of CAFs originate in bone marrow and are derived from mesenchymal stem cells [41].”
• Extracellular matrix: a dynamic niche component during cancer progression (2012, neutral): “The main contributors of altered activities of ECM remodeling enzymes and thus abnormal ECM metabolism are stromal cells, including cancer associated fibroblasts (CAFs) and immune cells (Bhowmick et al., 2004; Orimo et al., 2005).”
• Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential (2015, background): “We previously found that Grem1 expression identified the most clonogenic fraction of marrow stromal cultures (Quante et al., 2011).”
• Genetics and biology of prostate cancer (2018, background): “For example, MSCs can promote metastasis of breast, gastric, and prostate cancers (Karnoub et al. 2007; Quante et al. 2011; Jung et al. 2013).”
• Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives (2020, background): “While activated HSCs are the predominant precursor of myofibroblasts in fibrotic liver (>90% of collagen-producing cells), increasing evidence shows that myofibroblasts can also derive from portal fibroblasts [62,63], bone marrow [64,65], and some studies have suggested Epithelial-To-Mesenchymal Cel”
• Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. (2012, background): “The primary tumor signals to the bone marrow and stimulates the release of MSCs into the circulation, with recruitment by stromal cell–derived factor-1 chemokine gradients to the tumor site, where they are converted into myofibroblasts by TGF 1.(154) Moreover, osteopontin released by an aggressive x”