Heterogeneity of Circulating Tumor Cell Neoplastic Subpopulations Outlined by Single-Cell Transcriptomics.

Fatal metastasis occurs when circulating tumor cells (CTCs) disperse through the blood to initiate a new tumor at specific sites distant from the primary tumor. CTCs have been classically defined as nucleated cells positive for epithelial cell adhesion molecule and select cytokeratins (EpCAM/CK/DAPI), while negative for the common lymphocyte marker CD45. The enumeration of CTCs allows an estimation of the overall metastatic burden in breast cancer patients, but challenges regarding CTC heterogeneity and metastatic propensities persist, and their decryption could improve therapies. CTCs from metastatic breast cancer (mBC) patients were captured using the RareCyteTM Cytefinder II platform. The Lin- and Lin+ (CD45+) cell populations isolated from the blood of three of these mBC patients were analyzed by single-cell transcriptomic methods, which identified a variety of immune cell populations and a cluster of cells with a distinct gene expression signature, which includes both cells expressing EpCAM/CK ("classic" CTCs) and cells possessing an array of genes not previously associated with CTCs. This study put forward notions that the identification of these genes and their interactions will promote novel areas of analysis by dissecting properties underlying CTC survival, proliferation, and interaction with circulatory immune cells. It improves upon capabilities to measure and interfere with CTCs for impactful therapeutic interventions.

Mechanical, Cellular, and Proteomic Properties of Laryngotracheal Cartilage.

The larynx sometimes requires repair and reconstruction due to cancer resection, trauma, stenosis, or developmental disruptions. Bioengineering has provided some scaffolding materials and initial attempts at tissue engineering, especially of the trachea, have been made. The critical issues of providing protection, maintaining a patent airway, and controlling swallowing and phonation, require that the regenerated laryngotracheal cartilages must have mechanical and material properties that closely mimic native tissue. These properties are determined by the cellular and proteomic characteristics of these tissues. However, little is known of these properties for these specific cartilages. This review considers what is known and what issues need to be addressed.