EpCAM-positive disseminated cancer cells in bone marrow impact on survival of early-stage NSCLC patients.

Introduction: Detection of disseminated cancer cells (DCC) in bone marrow (BM) of patients with early-stage NSCLC has been associated with poor outcome. However, the phenotype, and hence relevant therapy targets, of DCCs in BM are unknown. We therefore compared a classical pan-Cytokeratin (CK) antibody for DCC detection with an anti-EpCAM antibody that may also detect more stem-like cells and tested whether assay positivity impacts on the survival of NSCLC patients.

Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency.

Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profile rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identify IL6/PI3K-signaling as candidate pathway for DCC activation. Surprisingly, and similar to mammary epithelial cells, DCCs lack membranous IL6 receptor expression and mechanistic dissection reveals IL6 trans-signaling to regulate a stem-like state of mammary epithelial cells via gp130.

Transcriptome asymmetry within mouse zygotes but not between early embryonic sister blastomeres.

Transcriptome regionalization is an essential polarity determinant among metazoans, directing embryonic axis formation during normal development. Although conservation of this principle in mammals is assumed, recent evidence is conflicting and it is not known whether transcriptome asymmetries exist within unfertilized mammalian eggs or between the respective cleavage products of early embryonic divisions. We here address this by comparing transcriptome profiles of paired single cells and sub-cellular structures obtained microsurgically from mouse oocytes and totipotent embryos.