Role of CTHRC1 in the Pathogenesis and Therapy of LAM

Awardee: Elizabeth Henske

Institution: BWH

Award Amount: $70,769

Funding Period: February 1, 2021 - January 31, 2022

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Summary:

This project is focused on a protein, CTHRC1 (collagen triple-helix repeat containing 1), that has never before been studied in LAM.  CTHRC1 is a protein that is usually secreted by cells and can be detected in the blood.  In other diseases, CTHRC1 is linked to the rate of cellular growth, and in several types of cancer, a high level of CTHRC1 in the blood is associated with a poor clinical prognosis.  

 In a new line of investigation in our lab, Dr. Nico Alesi has discovered that levels of CTHRC1 are elevated in cellular models of LAM.  CTHRC1 is also increased in human angiomyolipomas and in LAM cells.   Interestingly, levels of CTHRC1 are not suppressed by Rapamycin.  In TSC2-deficient cells, inhibition of CTHRC1 decreases cell growth. 

 These data suggest that CTHRC1 is a newly recognized driver of LAM cell growth.  Because levels of CTHRC1 are not affected by the mTOR inhibitor Rapamycin, CTHRC1 could help to explain why LAM cells are not eliminated during therapy with mTOR inhibitors.  Identifying therapeutic strategies to eliminate LAM cells is a key goal of this work.