Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells

Dhahri, Douaa; Sato-Kusubata, Kaori; Ohki-Koizumi, Makiko; Nishida, Chiemi; Tashiro, Yoshihiko; Munakata, Shinya; Shimazu, Hiroshi; Salama, Yousef; Eiamboonsert, Salita; Nakauchi, Hiromitsu; Hattori, Koichi; Heissig, Beate

doi:10.1182/blood-2015-10-673103

Cited by 18 publications

(22 citation statements)

References 46 publications

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“…Moreover, it has recently been shown that some fibrinolysis associated factors can also play an indirect role in HSC regulation by creating a more supportive microenvironment. For example, tissue plasminogen activator (tPA) has been demonstrated to induce the expansion of CD45 − TER119 − Sca‐1 + PDGFRα + mesenchymal stromal cells (PαS MSCs) in BM [Dhahri et al, ]. Mechanistically, tPA induces the release of kit ligand from PαS MSCs which activates c‐kit + endothelial cells to secrete platelet derived growth factor‐BB and fibroblastic growth factor‐2.…”

Section: Soluble Factors and Surface Proteinsmentioning

confidence: 99%

“…Mechanistically, tPA induces the release of kit ligand from PαS MSCs which activates c‐kit + endothelial cells to secrete platelet derived growth factor‐BB and fibroblastic growth factor‐2. As a positive feedback, PDGFRα expression is upregulated in PαS MSCs ultimately leading to cell expansion [Dhahri et al, ].…”

Section: Soluble Factors and Surface Proteinsmentioning

confidence: 99%

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Niche Extracellular Matrix Components and Their Influence on HSC

et al. 2017

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Maintenance of hematopoietic stem cells (HSC) takes place in a highly specialized microenvironment within the bone marrow. Technological improvements, especially in the field of in vivo imaging, have helped unravel the complexity of the niche microenvironment and have completely changed the classical concept from what was previously believed to be a static supportive platform, to a dynamic microenvironment tightly regulating HSC homeostasis through the complex interplay between diverse cell types, secreted factors, extracellular matrix molecules, and the expression of different transmembrane receptors. To add to the complexity, non-protein based metabolites have also been recognized as a component of the bone marrow niche. The objective of this review is to discuss the current understanding on how the different extracellular matrix components of the niche regulate HSC fate, both during embryonic development and in adulthood. Special attention will be provided to the description of non-protein metabolites, such as lipids and metal ions, which contribute to the regulation of HSC behavior. J. Cell. Biochem. 118: 1984-1993, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Soluble Factors and Surface Proteinsmentioning

confidence: 99%

Section: Soluble Factors and Surface Proteinsmentioning

confidence: 99%

Niche Extracellular Matrix Components and Their Influence on HSC

et al. 2017

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“…Propidium iodide fluorescence was measured and positive cells (dead cells) were excluded. MSC isolation and culture from bone marrow cells were performed, as described by Dhahri et al (27).…”

Section: Msc Analysismentioning

confidence: 99%

“…The tumor niche is recognized as a key factor in the multiple stages of cancer progression, mediating local resistance, immune escape, and metastasis (26). We showed that tPA can expand platelet-derived growth factor receptor (PDGFR) a-MSCs in noncancerous tissues (27).…”

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confidence: 99%

The fibrinolytic factor tPA drives LRP1‐mediated melanoma growth and metastasis

et al. 2018

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The multifunctional endocytic receptor low‐density lipoprotein receptor‐related protein (LRP)1 has recently been identified as a hub within a biomarker network for multicancer clinical outcome prediction. The mechanism how LRP1 modulates cancer progression is poorly understood. In this study we found that LRP1 and one of its ligands, tissue plasminogen activator (tPA), are expressed in melanoma cells and control melanoma growth and lung metastasis in vivo. Mechanistic studies were performed on 2 melanoma cancer cell lines, B16F10 and the B16F1 cells, both of which form primary melanoma tumors, but only B16F10 cells metastasize to the lungs. Tumor‐, but not niche cell‐derived tPA, enhanced melanoma cell proliferation in tPA−/− mice. Gain‐of‐function experiments revealed that melanoma LRP1 is critical for tumor growth, recruitment of mesenchymal stem cells into the tumor bed, and metastasis. Melanoma LRP1 was found to enhance ERK activation, resulting in increased matrix metalloproteinase (MMP)‐9 RNA, protein, and secreted activity, a well‐known modulator of melanoma metastasis. Restoration of LRP1 and tPA in the less aggressive, poorly metastatic B16F1 tumor cells enhanced tumor cell proliferation and led to massive lung metastasis in murine tumor models. Antimelanoma drug treatment induced tPA and LRP1 expression. tPA or LRP1 knockdown enhanced chemosensitivity in melanoma cells. Our results identify the tPA‐LRPl pathway as a key switch that drives melanoma progression, in part by modulating the cellular composition and proteolytic makeup of the tumor niche. Targeting this pathway may be a novel treatment strategy in combination treatments for melanoma.—Salama, Y., Lin, S.‐Y., Dhahri, D., Hattori, K., Heissig, B. The fibrinolytic factor tPA drives LRP1‐mediated melanoma growth and metastasis. FASEB J. 33, 3465–3480 (2019). http://www.fasebj.org

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“…1 T he bone marrow (BM) preserves long-term repopulating hematopoietic stem cells (LT-HSCs) for life-long blood cell production and immunity. Hematopoietic stem cells (HSCs) reside predominantly in perivascular niches formed by sinusoidal endothelial and mesenchymal cells.…”

Section: Wolfram Ruf Center For Thrombosis and Hemostasis Mainzmentioning

confidence: 99%

Hemostasis keeps the stem cell niche in order

Ruf¹

2016

Blood

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Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells

Cited by 18 publications

References 46 publications

Niche Extracellular Matrix Components and Their Influence on HSC

Niche Extracellular Matrix Components and Their Influence on HSC

The fibrinolytic factor tPA drives LRP1‐mediated melanoma growth and metastasis

Hemostasis keeps the stem cell niche in order

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