Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis
Technical Report,30 Sep 2014,29 Sep 2015
Baylor College of Medicine Houston United States
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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 Notch1HPSE combinations from metastatic HER2 breast cancer patients either with BCBM at clinical diagnosis. We used the DEPArrayTM, 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 DEPArrayTM-isolated EpCAM-negative CTC subsets, having Notch1 and HPSE expression and combinations thereof, to clinical BCBM. We will perform Notch1 and HPSE gainloss-of-expression studies using the 4 combinatorial Notch1HPSE CTC subsets and employing pINDUCER, a novel and potent inducible shRNAcDNA lentivirus to regulate Notch1HPSE 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.