LRRC33 is a novel binding and potential regulating protein of TGF-β1 function in human acute myeloid leukemia cells

Autoři: Wenjiang Ma aff001;  Yan Qin aff001;  Bjoern Chapuy aff002;  Chafen Lu aff001
Působiště autorů: Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA, United States of America aff001;  Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States of America aff002;  Harvard Medical School, Boston, MA, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


Transforming growth factor‑β1 (TGF-β1) is a versatile cytokine. It has context-dependent pro- and anti-cell proliferation functions. Activation of latent TGF-β1 requires release of the growth factor from pro-complexes and is regulated through TGF-β binding proteins. Two types of TGF-β binding partners, latent TGF-β-binding proteins (LTBPs) and leucine-rich-repeat-containing protein 32 (LRRC32), have been identified and their expression are cell specific. TGF-β1 also plays important roles in acute myeloid leukemia (AML) cells. However, the expression of LTBPs and LRRC32 are lacking in myeloid lineage cells and the binding protein of TGF-β1 in these cells are unknown. Here we show that a novel leucine-rich-repeat-containing protein family member, LRRC33, with high mRNA level in AML cells, to be the binding and regulating protein of TGF-β1 in AML cells. Using two representative cell lines MV4-11 and AML193, we demonstrate that the protein expression of LRRC33 and TGF-β1 are correlated. LRRC33 co-localizes and forms complex with latent TGF-β1 protein on the cell surface and intracellularly in these cells. Similar as in other cell types, the activation of TGF-β1 in MV4-11 and AML193 cells are also integrin dependent. We anticipate our study to be a starting point of more comprehensive research on LRRC33 as novel TGF-β regulating protein and potential non-genomic based drug target for AML and other myeloid malignancy.

Klíčová slova:

Acute myeloid leukemia – Cell binding – Cell staining – Flow cytometry – Immunoprecipitation – Protein complexes – TGF-beta signaling cascade – Integrins


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