Increased breast tissue stiffness is correlated with breast cancer risk and invasive cancer progression. However, its role in promoting bone metastasis, a major cause of mortality, is not yet understood. It is previously identified that the composition and stiffness of alginate‐based hydrogels mimicking normal (1–2 kPa) and cancerous (6–10 kPa) breast tissue govern phenotype of breast cancer cells (including MDA‐MB‐231) in vitro. Here, to understand the causal effect of primary tumor stiffness on metastatic potential, a new breast‐to‐bone in vitro model is described. Together with alginate‐gelatin hydrogels to mimic breast tissue, 3D printed biohybrid poly‐caprolactone (PCL)‐composite scaffolds, decellularized following bone‐ECM deposition through Saos‐2 engraftment, are used to mimic the bone tissue. It is reported that higher hydrogel stiffness results in the increased migration and invasion capacity of MDA‐MB 231 cells. Interestingly, increased expression of osteolytic factors PTHrP and IL‐6 is observed when MDA‐MB‐231 cells pre‐conditioned in stiffer hydrogels (10 kPa, 3% w/v gelatin) colonize the bone/PCL scaffolds. The new breast‐to‐bone in vitro models herein described are designed with relevant tissue microenvironmental factors and could emerge as future non‐animal technological platforms for monitoring metastatic processes and therapeutic efficacy.
In the main article from pages 120 to 127 of volume 86, issue 1 (January 2017) of Clinical Endocrinology, 1 the correct phrases are written below:• On page 121, under the section Statistical Analyses, this should be "HDL cholesterol <1.3 mmol L −1 in women (n = 430) and HDL cholesterol <1.0 mmol L −1 in men (n = 239)."• On page 124, under the section Effect of exclusion of participants with high-risk baseline lipid values from longitudinal regression analyses, itshould read "(β = 0.04, SE = 0.02, P = 003) could be detected in women (data not shown)."
This is a repository copy of Corrigendum to "Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands" [Canc. Lett. 403 (2017) 98-107].
Increased breast tissue stiffness is correlated with breast cancer risk and invasive cancer progression. However, its role in promoting bone metastasis, which shares a large burden of breast cancer deaths, has not yet been understood. To better understand the cause-effect relationship of tissue stiffness on breast cancer's metastatic potential, we fabricated three-dimensional (3D) models to mimic breast and bone tissue in vitro. Based on our previous work, we used alginate-based hydrogels allowing precise control over stiffness and composition of extracellular breast tissue matrix; and 3D printed poly-ε-caprolactone (PCL)-composite scaffolds to mimic the bone. The latter were further modified by promoting bone-ECM deposition using Saos-2 cells. After a decellularization step, PCL scaffolds were assembled with alginate-gelatin hydrogels and a novel breast-to-bone in vitro model was established. It was observed that increased stiffness of hydrogel resulted in higher migration and invasion capacity of MDA-MB 231 cells. Additionally, PTHrP and IL-6 expression, both of which are implicated in bone metastasis, were higher when cells from stiff hydrogels were cultured in bone/PCL scaffolds. These breast-to-bone in vitro models pose as a novel non-animal technology to pave the way for incorporating important tissue microenvironmental factors of the disease physiology (e.g. tissue stiffness) and emerge as promising future platforms for monitoring metastatic disease phenotypes and therapeutic efficacy.
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