The critical role of the bone microenvironment in cancer metastases

Casimiro, Sandra; Guise, Theresa A.; Chirgwin, John M.

doi:10.1016/j.mce.2009.07.004

Cited by 129 publications

(88 citation statements)

References 91 publications

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“…It has been documented that different types of cancer produce metastases at preferred secondary sites, depending on organ-susceptibility to specific cells. Stephen Paget proposed the 'seed and soil' theory that the molecular interactions between metastatic cells (seeds) and stromal microenvironment (soil) play critical roles throughout the multi-process of metastasis (25,26). In this study, we used a previously established multi-organ metastasis mouse model (13), in which cancer cells were inoculated directly into the tail vein that travels to the lungs.…”

Section: Discussionmentioning

confidence: 99%

“…These changes also reflect the interaction between cancer cells and the local or host cells in the 'microenvironment' of the organ. To form metastatic tumors in a certain organ, cancer cells when homing to this specific organ must interact with the host microenvironment (25)(26)(27). To do so, certain molecular programs in cancer cells are activated (25,27).…”

Section: Discussionmentioning

confidence: 99%

“…FGFR3, encoding a receptor tyrosine kinase for fibroblast growth factor, was reported to be overexpressed in ~15-20% cases of myeloma, or constituvely activated due to mutations in most of bladder cancers and other solid tumors, including lung cancers. Fibroblast growth factors (FGF) are bone-derived factors abundant in the bone environment (6,26), therefore it is reasonable that lung cancer cells highly expressing FGFR3 might be more selectively colonized in bone than in lung or liver. In addition, the FGF-FGFR3 signaling pathway via Ras-MAPK and PI3K in cancer cells may lead to enhanced cell proliferation and migration (reviewed in refs.…”

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confidence: 99%

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Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice

et al. 2012

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Abstract. Lung cancer is commonly associated with multiorgan metastasis, and the bone is a frequent metastatic site for lung cancer. However, the molecular mechanism of organspecific metastasis remains poorly understood. To elucidate this issue, we analyzed in this study genome-wide gene expression profiles of 15 metastatic lesions from three organs (bone, lung and liver) in a mouse model with multi-organ metastasis properties of human non-small cell lung cancer cells (ACC-LC319/ bone2), using a combination of laser-microbeam microdissection and DNA microarrays. We identified 299 genes that could potentially be involved in the organ-selective nature of lung cancer metastasis. Among them, 77 were bone-specifically expressed elements, including genes involved in cell adhesion, cytoskeleton/cell motility, extracellular matrix remodeling and cell-cell signaling as well as genes already known to be involved in the bone metastasis of breast cancers. Quantitative RT-PCR confirmed the specific upregulation of eight genes in bone metastasis tumors, suggesting that these genes may be involved in bone metastasis. Our findings should be helpful for a better understanding of the molecular aspects of the metastatic process in different organs, and could lead to molecular target-based anticancer drugs and prevention of metastasis, especially bone metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice

et al. 2012

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“…Osteoblastic lesions are characteristic of prostate cancer, while in breast cancer, osteolytic lesions are found in 80 % of patients with stage IV metastatic disease. Complex cross-talk between tumour cells and the bone microenvironment promotes an active cycle of bone metastases through multiple extracellular factors, probably also including nucleotides (see [448,449]). …”

Section: Bone Cancer and Multiple Myelomamentioning

confidence: 99%

Purinergic signalling in the musculoskeletal system

Burnstock

Arnett

Orriss

2013

Purinergic Signalling

109

114

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It is now widely recognised that extracellular nucleotides, signalling via purinergic receptors, participate in numerous biological processes in most tissues. It has become evident that extracellular nucleotides have significant regulatory effects in the musculoskeletal system. In early development, ATP released from motor nerves along with acetylcholine acts as a cotransmitter in neuromuscular transmission; in mature animals, ATP functions as a neuromodulator. Purinergic receptors expressed by skeletal muscle and satellite cells play important pathophysiological roles in their development or repair. In many cell types, expression of purinergic receptors is often dependent on differentiation. For example, sequential expression of P2X5, P2Y 1 and P2X2 receptors occurs during muscle regeneration in the mdx model of muscular dystrophy. In bone and cartilage cells, the functional effects of purinergic signalling appear to be largely negative. ATP stimulates the formation and activation of osteoclasts, the bone-destroying cells. Another role appears to be as a potent local inhibitor of mineralisation. In osteoblasts, the bone-forming cells, ATP acts via P2 receptors to limit bone mineralisation by inhibiting alkaline phosphatase expression and activity. Extracellular ATP additionally exerts significant effects on mineralisation via its hydrolysis product, pyrophosphate. Evidence now suggests that purinergic signalling is potentially important in several bone and joint disorders including osteoporosis, rheumatoid arthritis and cancers. Strategies for future musculoskeletal therapies might involve modulation of purinergic receptor function or of the ecto-nucleotidases responsible for ATP breakdown or ATP transport inhibitors.

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“…Bone is an intriguing microenvironment for tumor biology, and still remains largely unexplored [16]. This uniquely complex milieu is due not only to the calcified matrix but also to multiple types of constituting cells, including bone cells (osteocytes, osteoclasts and osteoblasts), hematopoietic cells, immune cells, stromal cells and endothelial cells [17]. Considerable research efforts have been devoted to characterizing this complex microenvironment and also to elucidating differential roles of individual cell types in their contribution to tumor growth and metastasis in bone [13].…”

Section: Introductionmentioning

confidence: 99%

Roles of Bone Marrow Cells in Skeletal Metastases: No Longer Bystanders

Park

Soki

McCauley

2011

Cancer Microenvironment

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Bone serves one of the most congenial metastatic microenvironments for multiple types of solid tumors, but its role in this process remains under-explored. Among many cell populations constituting the bone and bone marrow microenvironment, osteoblasts (originated from mesenchymal stem cells) and osteoclasts (originated from hematopoietic stem cells) have been the main research focus for pro-tumorigenic roles. Recently, increasing evidence further elucidates that hematopoietic lineage cells as well as stromal cells in the bone marrow mediate distinct but critical functions in tumor growth, metastasis, angiogenesis and apoptosis in the bone microenvironment. This review article summarizes the key evidence describing differential roles of bone marrow cells, including hematopoietic stem cells (HSCs), megakaryocytes, macrophages and myeloid-derived suppressor cells in the development of metastatic bone lesions. HSCs promote tumor growth by switching on angiogenesis, but at the same time compete with metastatic tumor cells for occupancy of osteoblastic niche. Megakaryocytes negatively regulate the extravasating tumor cells by inducing apoptosis and suppressing proliferation. Macrophages and myeloid cells have pro-tumorigenic roles in general, suggesting a similar effect in the bone marrow. Hematopoietic and stromal cell populations in the bone marrow, previously considered as simple by-standers in the context of tumor metastasis, have distinct and active roles in promoting or suppressing tumor growth and metastasis in bone. Further investigation on the extended roles of bone marrow cells will help formulate better approaches to treatment through improved understanding of the metastatic bone microenvironment.

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The critical role of the bone microenvironment in cancer metastases

Cited by 129 publications

References 91 publications

Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice

Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice

Purinergic signalling in the musculoskeletal system

Roles of Bone Marrow Cells in Skeletal Metastases: No Longer Bystanders

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