Epithelial-to-Mesenchymal Transition Drives Invasiveness of Breast Cancer Brain Metastases

(1) Background: an increasing number of breast cancer patients develop lethal brain metastases (BM). The complete removal of these tumors by surgery becomes complicated when cells infiltrate into the brain parenchyma. However, little is known about the nature of these invading cells in breast cancer brain metastasis (BCBM). (2) Methods: we use intravital microscopy through a cranial window to study the behavior of invading cells in a mouse model of BCBM. (3) Results: we demonstrate that BCBM cells that escape from the metastatic mass and infiltrate into brain parenchyma undergo epithelial-to-mesenchymal transition (EMT). Moreover, cells undergoing EMT revert to an epithelial state when growing tumor masses in the brain. Lastly, through multiplex immunohistochemistry, we confirm the presence of these infiltrative cells in EMT in patient samples. (4) Conclusions: together, our data identify the critical role of EMT in the invasive behavior of BCBM, which warrants further consideration to target those cells when treating BCBM

The crystal structure and Raman spectrum of the sodium salt of 5-Acetic acid hydantoin

The sodium salt of 5-acetic acid hydantoin (5AAH) was synthesized, and its crystal structure determined by single crystal X-ray diffraction. The material was found to exhibit rather unusual structural features. Firstly, contrarily to what is most common for hydantoins, the 5AAH molecules in the crystal bind the sodium ions through coordination via its oxygen atoms (instead of via a deprotonated ring nitrogen). In second place, the molecular formula of the salt is Na(5AAH) 2 , i.e. , the formal charge of the hydantoin in the crystal is −0.5 e . Finally, the conformation adopted by the 5AAH molecules in the crystal of the salt is neither the most stable conformer for the isolated molecule (and observed before in the gas phase of the compound), nor that present in the neat crystalline compound (most stable polymorph at room temperature). These results show that 5AAH is a structurally very versatile molecule, which is able to participate in strong intermolecular interactions that can supersede the intrinsic higher structural stability of the individual molecules and lead to selection of different higher energy conformers on formation of a crystalline phase. The Raman spectrum of the newly synthesized salt was also obtained and used to extract further struc- tural details of the crystal, in particular on the prevalent intermolecular interactions. The results (both structural and spectroscopic) obtained for the studied sodium salt of 5AAH are also compared with those relative to the neat 5AAH most stable crystalline polymorph at room temperature. To help the interpre- tation of the spectra, DFT(B3LYP)/6–311 ++ G (d,p) calculations were undertaken on simple models based on the structural elements of the crystals

Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior

Although biopsies and tumor resection are prognostically beneficial for glioblastomas (GBM), potential negative effects have also been suggested. Here, using retrospective study of patients and intravital imaging of mice, we identify some of these negative aspects, including stimulation of proliferation and migration of non-resected tumor cells, and provide a strategy to prevent these adverse effects. By repeated high-resolution intravital microscopy, we show that biopsy-like injury in GBM induces migration and proliferation of tumor cells through chemokine (C-C motif) ligand 2 (CCL-2)-dependent recruitment of macrophages. Blocking macrophage recruitment or administrating dexamethasone, a commonly used glucocorticoid to prevent brain edema in GBM patients, suppressed the observed inflammatory response and subsequent tumor growth upon biopsy both in mice and in multifocal GBM patients. Taken together, our study suggests that inhibiting CCL-2-dependent recruitment of macrophages may further increase the clinical benefits from surgical and biopsy procedures

Epithelial-to-Mesenchymal Transition Drives Invasiveness of Breast Cancer Brain Metastases

(1) Background: an increasing number of breast cancer patients develop lethal brain metastases (BM). The complete removal of these tumors by surgery becomes complicated when cells infiltrate into the brain parenchyma. However, little is known about the nature of these invading cells in breast cancer brain metastasis (BCBM). (2) Methods: we use intravital microscopy through a cranial window to study the behavior of invading cells in a mouse model of BCBM. (3) Results: we demonstrate that BCBM cells that escape from the metastatic mass and infiltrate into brain pa-renchyma undergo epithelial-to-mesenchymal transition (EMT). Moreover, cells undergoing EMT revert to an epithelial state when growing tumor masses in the brain. Lastly, through multiplex immunohistochemistry, we confirm the presence of these infiltrative cells in EMT in patient sam-ples. (4) Conclusions: together, our data identify the critical role of EMT in the invasive behavior of BCBM, which warrants further consideration to target those cells when treating BCBM