An in vitro hyaluronic acid hydrogel based platform to model dormancy in brain metastatic breast cancer cells.

Breast cancer cells (BCCs) can remain dormant at the metastatic site, which when revoked leads to formation of metastasis several years after the treatment of primary tumor. Particularly, awakening of dormant BCCs in the brain results in breast cancer brain metastasis (BCBrM) which marks the most advanced stage of the disease with a median survival period of ~4-16 months. However, our understanding of dormancy associated with BCBrM remains obscure, in part, due to the lack of relevant in vitro platforms to model dormancy associated with BCBrM.

Role of Surface Chemistry in Mediating the Uptake of Ultrasmall Iron Oxide Nanoparticles by Cancer Cells.

Ultrasmall iron oxide nanoparticles (USIONPs) (<4 nm) have recently attracted significant attention because of their potential as positive T magnetic resonance imaging (MRI) contrast agent contrary to larger superparamagnetic iron oxide nanoparticles (>6 nm) which act as negative T MRI contrast agents. However, studies on the cellular uptake behavior of these nanoparticles are very limited compared to their counterpart, larger-sized superparamagnetic iron oxide nanoparticles. In particular, the effects of specific nanoparticle parameters on the cellular uptake behavior of USIONPs by various cancer cells are not available.

Bioengineered models to study tumor dormancy.

The onset of cancer metastasis is the defining event in cancer progression when the disease is considered lethal. The ability of metastatic cancer cells to stay dormant for extended time periods and reawaken at later stages leading to disease recurrence makes treatment of metastatic disease extremely challenging. The tumor microenvironment plays a critical role in deciding the ultimate fate of tumor cells, yet the mechanisms by which this occurs, including dormancy, is not well understood.

A combined compression molding, heating, and leaching process for fabrication of micro-porous poly(ε-caprolactone) scaffolds.

Biomaterial scaffolds have been increasingly used for tissue engineering applications as well as three dimensional (3D) cell culture models. Herein, we report a simple procedure combining compression molding, heating, and leaching methods for the fabrication of 3D micro-porous poly(ε-caprolactone) (PCL) biomaterial scaffolds. In this procedure, PCL micro particles are mixed with NaCl of defined sizes and compression molded, followed by heating and subsequent leaching of NaCl particles.

The influence of matrix stiffness on the behavior of brain metastatic breast cancer cells in a biomimetic hyaluronic acid hydrogel platform.

Breast cancer brain metastasis marks the most advanced stage of breast cancer no longer considered curable with a median survival period of ∼4-16 months. Apart from the genetic susceptibility (subtype) of breast tumors, brain metastasis is also dictated by the biophysical/chemical interactions of tumor cells with native brain microenvironment, which remain obscure, primarily due to the lack of tunable biomimetic in vitro models. To address this need, we utilized a biomimetic hyaluronic acid (HA) hydrogel platform to elucidate the impact of matrix stiffness on the behavior of MDA-MB-231Br cells, a brain metastasizing variant of the triple negative breast cancer line MDA-MB-231.

Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis.

The progression of breast cancer from the primary tumor setting to the metastatic setting is the critical event defining Stage IV disease, no longer considered curable. The microenvironment at specific organ sites is known to play a key role in influencing the ultimate fate of metastatic cells; yet microenvironmental mediated-molecular mechanisms underlying organ specific metastasis in breast cancer are not well understood. This review discusses biomimetic strategies employed to recapitulate metastatic organ microenvironments, particularly, bone, liver, lung and brain to elucidate the mechanisms dictating metastatic breast cancer cell homing and colonization.