Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Soo Chin Lee
  • Prashant Kumar
  • Tuan Zea Tan
  • Majid Ebrahimi Warkiani
  • Samuel GW. Ow
  • Sayantani Nandi
  • Chwee Teck Lim
  • Jean Paul Thiery

Detail(s)

Original languageEnglish
Pages (from-to)15578-15593
Journal / PublicationOncotarget
Volume6
Issue number17
Online published6 May 2015
Publication statusPublished - 2015
Externally publishedYes

Link(s)

Abstract

Circulating tumor cells (CTCs) are considered as surrogate markers for prognosticating and evaluating patient treatment responses. Here, 226 blood samples from 92 patients with breast cancer, including patients with newly diagnosed or metastatic refractory cancer, and 16 blood samples from healthy subjects were cultured in laser-ablated microwells. Clusters containing an increasing number of cytokeratin-positive (CK+) cells appeared after 2 weeks, while most blood cells disappeared with time. Cultures were heterogeneous and exhibited two distinct subpopulations of cells: 'Small' (≤ 25 μm; high nuclear/cytoplasmic ratio; CD45-) cells, comprising CTCs, and 'Large' (> 25 μm; low nuclear/cytoplasmic ratio; CD68+ or CD56+) cells, corresponding to macrophage and natural killer-like cells. The Small cell fraction also showed copy number increases in six target genes (FGFR1, Myc, CCND1, HER2, TOP2A and ZNF217) associated with breast cancer. These expanded CTCs exhibited different proportions of epithelial-mesenchymal phenotypes and were transferable for further expansion as spheroids in serum-free suspension or 3D cultures. Cluster formation was affected by the presence and duration of systemic therapy, and its persistence may reflect therapeutic resistance. This novel and advanced method estimates CTC clonal heterogeneity and can predict, within a relatively short time frame, patient responses to therapy.

Research Area(s)

  • Breast cancer, circulating tumor cells, CTCs, enrichment

Citation Format(s)

Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy. / Khoo, Bee Luan; Lee, Soo Chin; Kumar, Prashant et al.

In: Oncotarget, Vol. 6, No. 17, 2015, p. 15578-15593.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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