RvD1 resolves CF airway pathogenesis and has therapeutic potential in CF lung disease.

BackgroundKindlin-1, − 2, and − 3 are the three members of the Kindlin family. They are best known as regulators of integrin functions, contributing to fundamental biological processes such as cell survival, adhesion and migration. Their deregulation leads to diverse pathologies including a broad range of cancers in which both, tumor-promoting and tumor-inhibiting functions have been described.MethodsTo better characterize Kindlins implication in breast cancer, in vitro experiments were performed in a series of cancer cell lines. We first assessed their expression profiles and subcellular distributions. Then, their involvement in breast cancer cell morphology, migration and invasion was verified by examining phenotypic changes induced by the depletion of either isoforms using RNA interference. An expression study was performed in a series of breast cancer patient derived xenografts (n = 58) to define the epithelial and stromal contribution of each Kindlin. Finally, we analyzed the expression levels of the three Kindlins in a large series of human breast tumors, at the RNA (n = 438) and protein (n = 129) levels and we evaluated their correlation with the clinical outcome.ResultsWe determined that Kindlin-1 and Kindlin-2, but not Kindlin-3, were expressed in breast tumor cells. We uncovered the compensatory roles of Kindlin-1 and -2 in focal adhesion dynamics and cell motility. Remarkably, Kindlin-2 had a predominant effect on cell spreading and Kindlin-1 on cell invasion. In line with these experimental observations, Kindlin-1 overexpression was associated with a worse patients’ outcome. Notably, Kindlin-3, expressed by tumor infiltrating leukocytes, also correlated with a poor prognosis of breast cancer patients.ConclusionThis study demonstrates that each one of the Kindlin family members has a different expression profile emphasizing their redundant and complementary roles in breast tumor cells. We highlight the specific link between Kindlin-1 and breast cancer progression. In addition, Kindlin-3 overexpression in the tumor microenvironment is associated with more aggressive breast tumors.These results suggest that Kindlins play distinctive roles in breast cancer. Kindlins may be useful in identifying breast cancer patients with a worst prognosis and may offer new avenues for therapeutic intervention against cancer progression.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0955-4) contains supplementary material, which is available to authorized users.

The development of low‐cost accessible technologies for rapid prototyping of mechanical components has democratised engineering tools for hobbyists and researchers alike. The development of analogous approaches to fabrication of soft‐matter, and biologically compatible materials containing living cells, is anticipated to be similarly enabling across multiple fields of biological research. LEGO toy construction bricks represent low‐cost, precision engineered, and versatile construction materials for rapid prototyping. This study demonstrates construction of a benchtop LEGO 3D bioprinter for additive layer manufacture of a 3D structure containing viable human skin cells within a hydrogel scaffold. 3D bioprinted structures are formed from the deposition of microfluidically generated bio‐ink droplets containing live keratinocyte skin cells, representing components toward an artificial skin model. Fluid flow rates and printer speed, together with bio‐ink gelation rate, determine droplet packing arrangement in the bioprinted structures. The printing of 3D structures containing multiple bio‐inks is demonstrated and live cells are imaged in the resulting bioprints. Fluid delivery can be achieved using LEGO pumps and readily available, or home‐3D‐printed, microfluidic components, therefore avoiding the need for any specialist microfluidic hardware. Build instructions are described to enable easy uptake, modification and improvement by other laboratories, as well provide an accessible platform for learning and education. Affordable, accessible, and easy to use tools for 3D bioprinting are anticipated to open opportunities for a greater number of research labs to work with 3D cell culture and bio‐printed materials, with bioprinting expected to assist in better understanding of disease, contribute to tissue engineering and repair, and enable personalised medicine through the printing of cultured patient cells. The presented approach is not only an easily accessible laboratory tool for bioprinting, but also provides a learning system for mechanical construction, robotics, coding, microfluidics and cell biology, making it a versatile platform for research, education, and science engagement.