Thomas R. Cox, Oct 2016
Our new article as part of a special issue of the Journal of Bone Oncology focusing on The role of the microenvironment in bone metastasis is now out:
This special series features 15 outstanding articles presenting updates of our current understanding of the roles of several different components, cell types and molecules in the development of tumour growth in bone. Coming from a number of renowned key researchers in the field the special series highlights the new discoveries and research angles in this exciting and ever changing area of research.
The series, edited by Ingunn Holen, covers both the clinical and a preclinical perspective, giving an in depth overview of the history of bone-targeted agents in cancer as well as the role of the microenvironment in bone metastasis and response to therapy.
Lysyl Oxidase and bone metastasis
Our article discusses the contribution of extracellular matrix remodeling in the transition from a primary to disseminated metastatic bone tumour. The review provides an overview of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche formation in breast cancer bone metastasis.
We conclude our discussion by posing what we see to be the key outstanding questions, including
- Why do certain cancer cell types preferentially home to bone?
- Specifically what is it about mineralized tissue that makes it such a favourable place to grow?
- Which occurs first – abnormal extracellular matrix (ECM) which drives oncogenic transformation, or cancerous cells which create abnormal ECM?
- Does bone remodelling need to, at least in part, occur before cancer cells can successfully colonise? Or, do cancer cells start the remodelling only when they arrive in the bone marrow. Or both?
- Do tumour-derived factors circulate the body and exert differing effects on ECM remodelling within different organs, or do particular tumour-secreted factors initiate specific cascade reactions and or other signalling in specific tissues?
- Are there any built-in mechanisms within the bone which may restrict, or accelerate aberrant ECM remodelling?
Most deaths from solid cancers occur as a result of secondary metastasis to distant sites. Bone is the most frequent metastatic site for many cancer types and can account for up to 80% of cancer-related deaths in certain tumours. The progression from a discrete solid primary tumour to devastating and painful bone metastases is a complex process involving multiple cell types and steps. There is increasing evidence that modulation of the extracellular matrix plays an important role in the lethal transition from a primary to disseminated metastatic bone tumour. This review provides an overview of the current understanding on the role of role of lysyl oxidase, the extracellular matrix and the pre-metastatic niche in bone metastasis
View the article on the ScienceDirect homepage (OpenAccess)
For readers without access, please contact me via my contact page
Gartland A, Erler JT and Cox TR. The Role of Lysyl Oxidase, the Extracellular Matrix and the Pre-Metastatic Niche in Bone Metastasis
Journal of Bone Oncology (2016) | doi: 10.1016/j.jbo.2016.04.001