Bone Endosteal Mimics Regulates Breast Cancer Development and Phenotype.

Bone is a frequent site for metastatic development in various cancer types, including breast cancer, with a grim prognosis due to the distinct bone environment. Despite considerable advances, our understanding of the underlying processes leading to bone metastasis progression remains elusive. Here, we applied a bioactive three-dimensional (3D) model capable of mimicking the endosteal bone microenvironment. MDA-MB-231 and MCF7 breast cancer cells were cultured on the scaffolds, and their behaviors and the effects of the biomaterial on the cells were examined over time. We demonstrated that close interactions between the cells and the biomaterial affect their proliferation rates and the expression of c-Myc, cyclin D, and KI67, leading to cell cycle arrest. Moreover, invasion assays revealed increased invasiveness within this microenvironment. Our findings suggest a dual role for endosteal mimicking signals, influencing cell fate and potentially acting as a double-edged sword, shuttling between cell cycle arrest and more active, aggressive states.

CD44 in Bone Metastasis Development: A Key Player in the Fate Decisions of the Invading Cells?

A participant in key developmental processes, the adhesion glycoprotein CD44 is also expressed in several types of malignancies and can promote metastasis. In addition, the expression of CD44 isoforms in different types of cancer such as prostate and breast cancers may facilitate bone metastases by enhancing tumorigenicity, osteomimicry, cell migration, homing to bone, and anchorage within the bone specialized domains. Moreover, there is evidence that the CD44-ICD fragments in breast cancer cells may promote the cells' osteolytic nature. Yet the mechanisms by which CD44 and its downstream effectors promote the establishment of these cells within the bone are not fully elucidated. In this review, we summarize the current data on the roles played by CD44 in cancer progression and bone metastasis and the possible effects of its interaction with the different components of the bone marrow milieu.

Wnt Signaling in the Development of Bone Metastasis.

Wnt signaling occurs through evolutionarily conserved pathways that affect cellular proliferation and fate decisions during development and tissue maintenance. Alterations in these highly regulated pathways, however, play pivotal roles in various malignancies, promoting cancer initiation, growth and metastasis and the development of drug resistance. The ability of cancer cells to metastasize is the primary cause of cancer mortality. Bone is one of the most frequent sites of metastases that generally arise from breast, prostate, lung, melanoma or kidney cancer. Upon their arrival to the bone, cancer cells can enter a long-term dormancy period, from which they can be reactivated, but can rarely be cured. The activation of Wnt signaling during the bone metastasis process was found to enhance proliferation, induce the epithelial-to-mesenchymal transition, promote the modulation of the extracellular matrix, enhance angiogenesis and immune tolerance and metastasize and thrive in the bone. Due to the complexity of Wnt pathways and of the landscape of this mineralized tissue, Wnt function during metastatic progression within bone is not yet fully understood. Therefore, we believe that a better understanding of these pathways and their roles in the development of bone metastasis could improve our understanding of the disease and may constitute fertile ground for potential therapeutics.

In vitro behavior of bioactive hybrid implant composed of additively manufactured titanium alloy lattice infiltrated with Mg-based alloy.

We have developed a novel bioactive hybrid metallic implant that integrates the beneficial characteristics of a permanent matrix and a biodegradable substance. Such a combination may generate a material system that evolves into a porous structure within weeks to months following implantation and can be used to form strong interfacial bonding and osseointegration for orthopedic and dental applications. Presently, traditional technologies such as casting, powder metallurgy and plastic forming have limited ability to produce the complex bioactive implant structures that are required in practical applications. The present study aimed to develop an innovative bioactive TiMg (BTiMg) hybrid system using a Ti-lattice (Ti-6Al-4 V) produced by an additive manufacturing (AM) process, in combination with a new Mg-based alloy (Mg-2.4%Nd -0.6%Y -0.3%Zr) as a biodegradable filling material. We evaluated the in-vitro behavior of the BTiMg system in a simulated physiological environment, along with cytotoxicity assessment. The microstructure was evaluated by scanning electron microscopy and X-ray diffraction, mechanical properties were examined in terms of compressive strength, environmental performance analysis was conducted by electrochemical testing using potentiodynamic polarization and impedance spectroscopy (EIS), and cytotoxicity characteristics were assessed by indirect cell viability analysis. The results demonstrated the feasibility to produce geometrically complex implants by AM technology, as well as the strength and non-cytotoxic effects of the BTiMg system. Benefits included a relatively high ultimate compressive strength (UCS) and a high yield point (YP), along with an adequate cell viability response in the range between 70 and 120%.

Aggressiveness of 4T1 breast cancer cells hampered by Wnt production-2 inhibitor nanoparticles: An in vitro study.

Polymeric nanoparticles may enable delivery of drugs with lower systemic toxicity to solid tumors. Wnt signaling are evolutionary conserved pathways, involved in proliferation and fate decisions. Alterations in Wnt signaling play a pivotal role in various cancer types that promote cancer initiation, growth, metastasis and drug resistance. We designed a new strategy to allow an efficient targeting of both the canonical and the non-canonical Wnt pathways using nanoparticles loaded with inhibitor of Wnt productions-2 (IWP-2). This hydrophobic drug was successfully co-assembled into NPs composed of poly gamma-glutamic acid and a cationic and amphiphilic b-sheet peptide. Aggressive 4T1 breast cancer cells that were treated with IWP-2 loaded NPs gained a significant decrease in tumorigenic capacities attributed to improved IWP solubility, cellular uptake and efficacy.