Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth
| Autor: | Lina Wang, Ningzheng Dong, Yizhi Jiang, Xiaofei Qi, Yae Hu, Ruhong Yan, Can Wang, Quansheng Zhou, Qingyu Wu, Meng Liu |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cancer Research Neutrophils THP-1 Cells type II transmembrane serine protease (TTSP) Chronic lymphocytic leukemia Monocytes Jurkat Cells Mice 0302 clinical medicine hemic and lymphatic diseases Acute myeloid leukemia (AML) Original Research Cancer Biology Myeloid leukemia lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Leukemia Myeloid Acute medicine.anatomical_structure Oncology human airway trypsin‐like protease 4 (HAT‐L4) 030220 oncology & carcinogenesis Matrix Metalloproteinase 2 Proteases HL-60 Cells lcsh:RC254-282 03 medical and health sciences Cell Line Tumor Acute lymphocytic leukemia parasitic diseases medicine Animals Humans Radiology Nuclear Medicine and imaging business.industry Membrane Proteins matrix metalloproteinase (MMP) medicine.disease cancer progression Minimal residual disease 030104 developmental biology Cancer cell Cancer research Ectopic expression Bone marrow Serine Proteases K562 Cells business Neoplasm Transplantation HeLa Cells |
| Zdroj: | Cancer Medicine Cancer Medicine, Vol 8, Iss 5, Pp 2348-2359 (2019) |
| ISSN: | 2045-7634 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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