Cancer Med. 2019 Mar 7. doi: 10.1002/cam4.2074. [Epub ahead of print]
Yan R1,2, Liu M1, Hu Y1, Wang L1, Wang C1, Jiang Y1, Zhou Q1, Qi X1,3,4, Dong N1,3,5, Wu Q1,5,6.
Author Information
1Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
2Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
3MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, Suzhou, China.
4Department of Urology of the First Affiliated Hospital of Soochow University, Suzhou, China.
5Jiangsu Key Laboratory of Preventive and Translational Medicine of Geriatric Disease, Suzhou, China.
6Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, Ohio.
Abstract
Transmembrane serine proteases have been implicated in the development and progression of solid and hematological cancers. Human airway trypsin-like protease 4 (HAT-L4) is a transmembrane serine protease expressed in epithelial cells and exocrine glands. In the skin, HAT-L4 is important for normal epidermal barrier function. Here, we report an unexpected finding of ectopic HAT-L4 expression in neutrophils and monocytes from acute myeloid leukemia (AML) patients. Such expression was not detected in bone marrow cells from normal individuals or patients with chronic myeloid leukemia, acute lymphocytic leukemia and chronic lymphocytic leukemia. In AML patients who underwent chemotherapy, persistent HAT-L4 expression in bone marrow cells was associated with minimal residual disease and poor prognostic outcomes. In culture, silencing HAT-L4 expression in AML-derived THP-1 cells by short hairpin RNAs inhibited matrix metalloproteinase-2 activation and Matrigel invasion. In mouse xenograft models, inhibition of HAT-L4 expression reduced the proliferation and growth of THP-1 cell-derived tumors. Our results indicate that ectopic HAT-L4 expression is a pathological mechanism in AML and that HAT-L4 may be used as a cell surface marker for AML blast detection and targeting.