Substrate Stiffness Coupling TGF-β1 Modulates Migration and Traction Force of MDA-MB-231 Human Breast Cancer Cells in Vitro

Cancer cell migration is the hallmark of tumor metastasis; however, the mechanisms of cancer cell migration have not been fully understood. Considering the fact that biophysical and biochemical properties of the tumor microenvironment are altered during tumor progression, it is instinctive to think about whether the changed microenvironment can regulate cancer cell migration. Herein, we cultured human breast cancer cells (MDA-MB-231) on polyacrylamide gel substrates with different stiffnesses (1, 5, 10, and 20 kPa) with and without transforming growth factor-β1 (TGF-β1, 2 ng/mL) treatment to evaluate the effects of the altered tumor microenvironment on cancer cell migration in addition to the response of traction force generation and cytoskeleton remodeling. The results demonstrated that MDA-MB-231 migration increased with increasing substrate stiffness and was further enhanced with TGF-β1 addition. Traction forces and cytoskeleton remodeling were also found to be enhanced in response to TGF-β1 treatment. Furthermore, inhibiting myosin IIA-mediated contraction by blebbistatin decreased TGF-β1-enhanced traction force but increased TGF-β1-enhanced migration. These results imply that both biophysical (like stiffness) and biochemical (like TGF-β1) factors could orthogonally regulate cancer cell migration

Extracellular Biocoordinated Zinc Nanofibers Inhibit Malignant Characteristics of Cancer Cell

Inhibition of the heat shock proteins (HSPs) has been considered to be one of the promising strategies for cancer treatment. However, developing highly effective HSP inhibitors remains a challenge. Recent studies on the evolutionarily distinct functions between intracellular and extracellular HSPs (eHSPs) trigger a new direction with eHSPs as chemotherapeutic targets. Herein, the first engineered eHSP nanoinhibitor with high effectiveness is reported. The zinc–aspartic acid nanofibers have specific binding ability to eHSP90, which induces a decrease in the level of the tumor marker-gelatinases, consequently resulting in downregulation of the tumor-promoting inflammation nuclear factor-kappa B signaling, and finally inhibiting cancer cell proliferation, migration, and invasion; while they are harmless to normal cells. Our findings highlight the potential for cancer treatment by altering the key determinants that shape its ability to adapt and evolve using novel nanomaterials