title: Functional analysis of single cells identifies a rare subset of circulating tumor cells with malignant traits.
abstract: Ample evidence supports genetic and functional heterogeneity in primary tumors, but it remains unclear whether circulating tumor cells (CTCs) also exhibit the same hierarchical organization. We examined the functional diversity of viable, single CTCs using an array of subnanoliter wells (nanowells). The compartmentalization of single cells by nanowells allowed clonal comparison and mapping of heterogeneity of single cells or preformed clusters of cells. By measuring the short-term viability, invasiveness and secretory profiles of individual CTCs, it was evident that only a rare subset of CTCs possessed malignant traits indicative of metastatic potential in late-stage, progressing metastatic castration-resistant prostate cancer (mCRPC) patients. These CTCs were resistant to anoikis after being in the circulation, were invasive in their epithelial state, or secreted proteases capable of cleaving peptide substrates. Every CTC observed, however, did not exhibit such metastatic potential, suggesting that enumeration of CTCs alone may be insufficient to understand metastasis or stratify patients.
authors: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors: Xiaosai
authors: X
authors: Yao
authors: Atish D
authors: AD
authors: Choudhury
authors: Yvonne J
authors: YJ
authors: Yamanaka
authors: Viktor A
authors: VA
authors: Adalsteinsson
authors: Todd M
authors: TM
authors: Gierahn
authors: Christina A
authors: CA
authors: Williamson
authors: Carla R
authors: CR
authors: Lamb
authors: Mary-Ellen
authors: ME
authors: Taplin
authors: Mari
authors: M
authors: Nakabayashi
authors: Matthew S
authors: MS
authors: Chabot
authors: Tiantian
authors: T
authors: Li
authors: Gwo-Shu M
authors: GS
authors: Lee
authors: Jesse S
authors: JS
authors: Boehm
authors: Philip W
authors: PW
authors: Kantoff
authors: William C
authors: WC
authors: Hahn
authors: K Dane
authors: KD
authors: Wittrup
authors: J Christopher
authors: JC
authors: Love
mesh_terms: D023102:Anoikis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D036103:Nanotechnology / Q000379:methods*; D009363:Neoplasm Proteins / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D009363:Neoplasm Proteins