Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an Interleukin 8-dependent survival of leukemia cells

Abstract

a b s t r a c tChronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Bcr-Abl oncoprotein with constitutive tyrosine kinase activity. Exosomes are nanovesicles released by cancer cells that are involved in cell-to-cell communication thus potentially affecting cancer progression. It is well known that bone marrow stromal microenvironment contributes to disease progression through the establishment of a bi-directional crosstalk with cancer cells. Our hypothesis is that exosomes could have a functional role in this crosstalk. Interleukin-8 (IL 8) is a proinflammatory chemokine that activates multiple signalling pathways downstream of two receptors (CXCR1 and CXCR2). We demonstrated that exosomes released from CML cells stimulate bone marrow stromal cells to produce IL 8 that, in turn, is able to modulate both in vitro and in vivo the leukemia cell malignant phenotype.

WEHI-3 cells inhibit adipocyte differentiation in 3T3-L1 cells

“…Multiple studies have focused on the role of the BM microenvironment in the pathophysiology of hematological malignancies [19,20]. However, a growing body of evidence suggests that tumors can also regulate their surrounding microenvironment, making it more amenable to their survival and development [21,22]. For instance, AML cells can induce the expression and secretion of the Axl ligand Gas6 in BM-derived stromal cells, and Gas6, in turn, can mediate the proliferation, survival and chemoresistance of Axl-expressing AML cells [23].…”

The role of microenvironment and immunity in drug response in leukemia

“…Asparaginase is routinely used in the treatment of childhood acute lymphoblastic leukemia (ALL) due to the fact that ALL cells often depend on exogenous asparagine, as their own capacity for its production is generally low [62]. Despite this, however, not all patients respond to this therapy, which indicates there are further sources of asparagine production and potential interference with asparaginase treatment.…”

Natural Compounds: Molecular Weapons against Leukemia’s

“…Accumulating evidence demonstrated that cancer cells release higher levels of exosomes suggesting their involvement in cancer progression and microenvironment education [7,8]. Leukemia derived exosomes can also affect bone marrow microenvironment thus enhancing leukemia cell growth [9][10][11]. We will discuss the anticancer effects of plants extracellular vesicles in a following section.…”