Abstract
Bone is the primary site where some cancers develop secondary growth, particularly those derived from breast and prostate tissue. The spread of metastasis to distant sites relies on complex mechanisms by which only cells endowed with certain characteristics are able to reach secondary growth sites. Platelets play a pivotal role in tumour growth, by conferring resistance to shear stress to the circulating tumour cells and protection against natural killer cell attack. Mature polyploid megakaryocytes (MKs) reside in close proximity to the vascular sinusoids of bone marrow, where their primary function is to produce platelets. Emerging evidence has demonstrated that MKs are essential for skeletal homeostasis, due to the expression and production of the bone-related proteins osteocalcin, osteonectin, bone morphogenetic protein, osteopontin, bone sialoprotein, and osteoprotegerin. Debate surrounds the role that MKs play in the development of bone metastasis, which is the topic of this mini-review.
Highlights
Megakaryocytes (MKs), polyploid cells derived from bone marrow-residing hematopoietic stem cells (HSC) in response to thrombopoietin (TPO), are responsible for the production of platelets through a complicated regulatory mechanism
The aim of this review is to provide a brief overview of the involvement of MKs in bone metastasis, and to integrate the data from the literature with my observations from studies in which I have focused on the role of MKs in bone marrow and in the bone microenvironment following the engraftment of cancer cells
In the context of our studies, in which we investigate the complex network of signalling in the bone metastasis microenvironment and the part that microenvironment plays in influencing metastatic growth, MKs provide an important source of biological stimuli, for the composition of platelet cargo, and for the growth of metastatic cells
Summary
Megakaryocytes (MKs), polyploid cells derived from bone marrow-residing hematopoietic stem cells (HSC) in response to thrombopoietin (TPO), are responsible for the production of platelets through a complicated regulatory mechanism. A complex network of cellular interactions and the typesetting of the extracellular matrix (ECM) may be responsible for the differentiation and maturation of MKs in bone marrow, where the microenvironment is a key factor in megakaryopoiesis. As MKs have a central role in the regulation of bone mass and a strategic position in bone marrow, they have come into the focus of recent research on their possible involvement in the development of bone metastasis. The aim of this review is to provide a brief overview of the involvement of MKs in bone metastasis, and to integrate the data from the literature with my observations from studies in which I have focused on the role of MKs in bone marrow and in the bone microenvironment following the engraftment of cancer cells
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