TY - JOUR
T1 - Damage and Recovery of the Bone Marrow Microenvironment Induced by Cancer Chemotherapy - Potential Regulatory Role of Chemokine CXCL12/Receptor CXCR4 Signalling
AU - Georgiou, Kristen
AU - Foster, Bruce
AU - Xian, Cory
PY - 2010
Y1 - 2010
N2 - The bone marrow microenvironment houses haematopoietic stem cells (HSC), mesenchymal stem cells (MSC) and their progeny, supports haematopoiesis, osteogenesis, osteoclastogenesis, and adipogenesis. It plays a key role in maintaining homeostatic production of erythroid, myeloid or lymphoid cells, appropriate bone mass and bone health throughout life. Through cell-cell adhesion and chemotactic axes, a reciprocal inter-dependent relationship exists between these two cell lineages. Following chemotherapy-induced myelosuppression observed in cancer patients, HSCs are induced to enter into the cell cycle in order to reestablish the damaged microenvironment. These cells not only have the capacity to mobilise to the peripheral blood, but the ability to repopulate the marrow cavity as required. However, depending on the dosage and length of chemotherapy treatment, complications in bone and bone marrow recovery occur. This may manifest as marrow haematopoietic depletion, high marrow fat content, reduced bone formation and aggravated osteoclastic bone resorption. Although the molecular and cellular mechanisms governing injured states of the marrow microenvironment are yet to be fully elucidated, many reports have demonstrated the CXCL12/CXCR4 axis plays an important role in regulating the two cell lineages. Their interaction maintains bone marrow homeostasis and orchestrates its regeneration following chemotherapy. This review explores movement of MSC and HSC, haematopoiesis, commitment of osteoblasts, osteoclasts, and adipocytes, as well as the major signalling pathways that regulate these cellular processes under chemotherapy-treated conditions. This review also discusses molecular targets that are being used clinically or are currently under investigation for preserving the bone marrow microenvironment during or enhancing recovery after chemotherapy.
AB - The bone marrow microenvironment houses haematopoietic stem cells (HSC), mesenchymal stem cells (MSC) and their progeny, supports haematopoiesis, osteogenesis, osteoclastogenesis, and adipogenesis. It plays a key role in maintaining homeostatic production of erythroid, myeloid or lymphoid cells, appropriate bone mass and bone health throughout life. Through cell-cell adhesion and chemotactic axes, a reciprocal inter-dependent relationship exists between these two cell lineages. Following chemotherapy-induced myelosuppression observed in cancer patients, HSCs are induced to enter into the cell cycle in order to reestablish the damaged microenvironment. These cells not only have the capacity to mobilise to the peripheral blood, but the ability to repopulate the marrow cavity as required. However, depending on the dosage and length of chemotherapy treatment, complications in bone and bone marrow recovery occur. This may manifest as marrow haematopoietic depletion, high marrow fat content, reduced bone formation and aggravated osteoclastic bone resorption. Although the molecular and cellular mechanisms governing injured states of the marrow microenvironment are yet to be fully elucidated, many reports have demonstrated the CXCL12/CXCR4 axis plays an important role in regulating the two cell lineages. Their interaction maintains bone marrow homeostasis and orchestrates its regeneration following chemotherapy. This review explores movement of MSC and HSC, haematopoiesis, commitment of osteoblasts, osteoclasts, and adipocytes, as well as the major signalling pathways that regulate these cellular processes under chemotherapy-treated conditions. This review also discusses molecular targets that are being used clinically or are currently under investigation for preserving the bone marrow microenvironment during or enhancing recovery after chemotherapy.
KW - Adipocytes
KW - Bone marrow microenvironment
KW - Cancer chemotherapy
KW - CXCL12
KW - Haematopoietic stem cell (HSC)
KW - Mesenchymal stem cell (MSC)
KW - Osteoblasts
KW - Stem cell niche
UR - http://www.scopus.com/inward/record.url?scp=77954705144&partnerID=8YFLogxK
U2 - 10.2174/156652410791608243
DO - 10.2174/156652410791608243
M3 - Article
VL - 10
SP - 440
EP - 453
JO - CURRENT MOLECULAR MEDICINE
JF - CURRENT MOLECULAR MEDICINE
SN - 1566-5240
IS - 5
ER -