Tsc2 disruption in mesenchymal progenitors results in tumors with vascular anomalies overexpressing Lgals3

Peter J. Klover, Rajesh L. Thangapazham, Jiro Kato, Ji An Wang, Stasia A. Anderson, Victoria Hoffmann, Wendy K. Steagall, Shaowei Li, Elizabeth McCart, Neera Nathan, Joshua D. Bernstock, Matthew D. Wilkerson, Clifton L. Dalgard, Joel Moss, Thomas N. Darling*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Increased mTORC1 signaling from TSC1/TSC2 inactivation is found in cancer and causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in TSC tumorigenesis was investigated through disruption of Tsc2 in craniofacial and limb bud mesenchymal progenitors. Tsc2cKOPrrx1-cre mice had shortened lifespans and extensive hamartomas containing abnormal tortuous, dilated vessels prominent in the forelimbs. Abnormalities were blocked by the mTORC1 inhibitor sirolimus. A Tsc2/mTORC1 expression signature identified in Tsc2-deficient fibroblasts was also increased in bladder cancers with TSC1/ TSC2 mutations in the TCGA database. Signature component Lgals3 encoding galectin-3 was increased in Tsc2-deficient cells and serum of Tsc2cKOPrrx1-cre mice. Galectin-3 was increased in TSC-related skin tumors, angiomyolipomas, and lymphangioleiomyomatosis with serum levels in patients with lymphangioleiomyomatosis correlating with impaired lung function and angiomyolipoma presence. Our results demonstrate Tsc2-deficient mesenchymal progenitors cause aberrant morphogenic signals, and identify an expression signature including Lgals3 relevant for human disease of TSC1/TSC2 inactivation and mTORC1 hyperactivity.

Original languageEnglish
Article numbere23202
StatePublished - 11 Jul 2017
Externally publishedYes


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