Exosomes promote bone marrow angiogenesis in hematologic neoplasia: the role of hypoxia.

PURPOSE OF REVIEW: To review the data on angiogenesis related to exosomes secreted by tumor cells in hematologic neoplasia and to elucidate the role of exosomes and exosomal miRNA in the bone marrow microenvironment, especially under hypoxic conditions.

RECENT FINDINGS: Cross-talk between bone marrow tumor cells and surrounding cells, including endothelial cells, is important for tumor growth in hematologic neoplasia. In addition to conventional signaling pathways, exosomes, which are small endosome-derived vesicles containing miRNAs, can help to modulate the microenvironment without directly contacting nontumorous cells. The human myeloid leukemia cell line K562 secretes exosomes containing a large amount of miR-92a that enhances angiogenesis under normoxic and hypoxic conditions. With chronic hypoxia, exosomes secreted by multiple myeloma cells also enhance angiogenesis by targeting factor-inhibiting hypoxia-inducible factor-1 via miR-135b.

SUMMARY: Intercellular communication between tumor cells and a heterogeneous population of bone marrow stromal cells is mediated by exosomes containing various functional proteins, mRNA, and miRNA. Hypoxia is a major regulator of exosomal content and affects angiogenesis in various types of hematologic neoplasia. Functional analysis of exosomes and exosome-mediated cell-cell interactions not only clarifies molecular pathogenesis but also suggests new treatment strategies for hematologic neoplasia through targeting exosomes.