Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis
Abstract
Breast cancer brain metastasis (BCBM) is devastating and increasing in frequency, however, BCBM mechanisms are understudied and remain largely unknown. Further, although notions that circulating tumor cells (CTCs) acting as seedsof intractable metastasis are established, virtually nothing is known about the properties and biomarkers of BCBM colonizing CTCs. We hypothesized that Notch1 and HPSE are novel CTC biomarkers to predict the presence of primary breast cancer brain metastasis; and they can be potential therapeutic targets to prevent secondary BCBM. Accordingly, we isolated CTC subsets expressing Notch1/HPSE combinations from metastatic HER2+ breast cancer patients either with BCBM at clinical diagnosis. We used the DEPArray(TM), a new image-based CTC platform capable of isolating viable CTCson a cell per cell basis, the smallest functional unit of cancer. We will directly link DEPArray(TM)-isolated EpCAM-negative CTC subsets, having Notch1 and HPSE expression and combinations thereof, to clinical BCBM. =We will perform Notch1 and HPSE gain/loss-of-expression studies using the 4 combinatorial Notch1/HPSE CTC subsets; and employing pINDUCER, a novel and potent inducible shRNA/cDNA lentivirus to regulate Notch1/HPSE gene expression and BCBM development. We aim to demonstrate that the expression of Notch1 and HPSE axis in CTC subsets is directly related to, and critical for, CTC-induced BCBM onset.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1003310
Entities
People
- Dario Marchetti
Organizations
- Baylor College of Medicine