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

Transforming growth factor - {beta}1 (TGF-{beta}1) is a versatile cytokine. It has context-dependent pro- and anti-cell proliferation functions. Activation of latent TGF-{beta}1 requires release of the growth factor from pro-complexes and is regulated through TGF-{beta} binding proteins. Two types of TGF-{beta} binding partners, latent TGF-{beta}-binding proteins (LTBPs) and leucine-rich-repeat-containing protein 32 (LRRC32), have been identified and their expression are cell specific. TGF-{beta}1 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-{beta}1 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-{beta}1 in AML cells. Using two representative cell lines MV4-11 and AML193, we demonstrate that the protein expression of LRRC33 and TGF-{beta}1 are correlated. LRRC33 co-localizes and forms complex with latent TGF-{beta}1 protein on the cell surface and intracellularly in these cells. Similar as in other cell types, the activation of TGF-{beta}1 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-{beta} regulating protein and potential non-genomic based drug target for AML and other myeloid malignancy.