• Home
  • Search Results
  • Acute tissue injury activates satellite cells and promotes sarcoma formation via the HGF/c-MET signaling pathway.

Acute tissue injury activates satellite cells and promotes sarcoma formation via the HGF/c-MET signaling pathway.

Cancer research (2014-12-17)
David Van Mater, Leonor Añó, Jordan M Blum, Micah T Webster, WeiQiao Huang, Nerissa Williams, Yan Ma, Diana M Cardona, Chen-Ming Fan, David G Kirsch
ABSTRACT

Some patients with soft-tissue sarcoma (STS) report a history of injury at the site of their tumor. Although this phenomenon is widely reported, there are relatively few experimental systems that have directly assessed the role of injury in sarcoma formation. We recently described a mouse model of STS whereby p53 is deleted and oncogenic Kras is activated in muscle satellite cells via a Pax7(CreER) driver following intraperitoneal injection with tamoxifen. Here, we report that after systemic injection of tamoxifen, the vast majority of Pax7-expressing cells remain quiescent despite mutation of p53 and Kras. The fate of these muscle progenitors is dramatically altered by tissue injury, which leads to faster kinetics of sarcoma formation. In adult muscle, quiescent satellite cells will transition into an active state in response to hepatocyte growth factor (HGF). We show that modulating satellite cell quiescence via intramuscular injection of HGF increases the penetrance of sarcoma formation at the site of injection, which is dependent on its cognate receptor c-MET. Unexpectedly, the tumor-promoting effect of tissue injury also requires c-Met. These results reveal a mechanism by which HGF/c-MET signaling promotes tumor formation after tissue injury in a mouse model of primary STS, and they may explain why some patients develop a STS at the site of injury.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tamoxifen, ≥99%
Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
2-Methylbutane, ReagentPlus®, ≥99%
Sigma-Aldrich
2,2,2-Tribromoethanol, 97%
Sigma-Aldrich
2-Methyl-2-butanol, ReagentPlus®, 99%
Sigma-Aldrich
2-Methylbutane, anhydrous, ≥99%
Sigma-Aldrich
2-Methylbutane, suitable for HPLC, ≥99.5%
Sigma-Aldrich
2-Methyl-2-butanol, ReagentPlus®, ≥99%
Sigma-Aldrich
2-Methyl-2-butanol, anhydrous, ≥99%
Sigma-Aldrich
2-Methylbutane, ReagentPlus®, ≥99%
Supelco
Tamoxifen, analytical standard
Supelco
2-Methyl-2-butanol, analytical standard
Sigma-Aldrich
2-Methylbutane, puriss. p.a., ≥99.5% (GC)
Sigma-Aldrich
β-D-Allose, rare aldohexose sugar
Supelco
2-Methylbutane, analytical standard