Size-based detection of sarcoma circulating tumor cells and cell clusters

Masanori Hayashi, Peixuan Zhu, Gregory McCarty, Christian F. Meyer, Christine A. Pratilas, Adam Levin, Carol D. Morris, Catherine M. Albert, Kyle W. Jackson, Cha Mei Tang, David M. Loeb

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Metastatic disease is the most important factor in determining the survival of sarcoma patients. Since sarcoma metastasis is predominantly hematogenous, we hypothesized that detection and quantification of circulating tumor cells (CTCs) could reflect response to therapy and risk of metastatic relapse. We evaluated the presence of CTCs using a novel animal model and in the blood of patients with high grade sarcomas utilizing the CellSieve™ size-based low pressure microfiltration system. Sarcoma CTCs were identified based on antibody staining patterns and nuclear morphology. Additionally, RNA was extracted from the CTCs for molecular analysis including demonstration of an EWS-FLI1 translocation, identification of a previously unrecognized p53 mutation in a patient with Ewing sarcoma, and single cell RNA sequencing of CTC from a child with alveolar rhabdomyosarcoma. In mouse xenograft models, the presence of CTC correlates with disease burden and with clinically silent metastases. In human patients, CTCs were readily detected at diagnosis, decreased with successful treatment, and were detectable in the blood of patients with no radiographic evidence of disease prior to the development of overt metastasis. Although evaluation of CTC is established in the care of patients with carcinomas, this technology has yet to be effectively applied to the evaluation and treatment of sarcoma patients. Our work demonstrates that the CellSieve™ microfiltration system can be used to study the biology of CTC in both mouse models and human sarcoma patients, with the potential for application to the monitoring of disease response and prediction of metastatic relapse.

Original languageEnglish (US)
Pages (from-to)78965-78977
Number of pages13
JournalOncotarget
Volume8
Issue number45
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Circulating Neoplastic Cells
Sarcoma
Neoplasm Metastasis
Alveolar Rhabdomyosarcoma
RNA Sequence Analysis
Recurrence
Ewing's Sarcoma
Heterografts
Patient Care
Therapeutics
Animal Models
RNA
Staining and Labeling
Technology
Carcinoma
Pressure
Mutation

Keywords

  • Animal models
  • Biomarker
  • Circulating
  • Neoplastic cells
  • Xenograft

ASJC Scopus subject areas

  • Oncology

Cite this

Hayashi, M., Zhu, P., McCarty, G., Meyer, C. F., Pratilas, C. A., Levin, A., ... Loeb, D. M. (2017). Size-based detection of sarcoma circulating tumor cells and cell clusters. Oncotarget, 8(45), 78965-78977. https://doi.org/10.18632/oncotarget.20697

Size-based detection of sarcoma circulating tumor cells and cell clusters. / Hayashi, Masanori; Zhu, Peixuan; McCarty, Gregory; Meyer, Christian F.; Pratilas, Christine A.; Levin, Adam; Morris, Carol D.; Albert, Catherine M.; Jackson, Kyle W.; Tang, Cha Mei; Loeb, David M.

In: Oncotarget, Vol. 8, No. 45, 01.01.2017, p. 78965-78977.

Research output: Contribution to journalArticle

Hayashi, M, Zhu, P, McCarty, G, Meyer, CF, Pratilas, CA, Levin, A, Morris, CD, Albert, CM, Jackson, KW, Tang, CM & Loeb, DM 2017, 'Size-based detection of sarcoma circulating tumor cells and cell clusters', Oncotarget, vol. 8, no. 45, pp. 78965-78977. https://doi.org/10.18632/oncotarget.20697
Hayashi M, Zhu P, McCarty G, Meyer CF, Pratilas CA, Levin A et al. Size-based detection of sarcoma circulating tumor cells and cell clusters. Oncotarget. 2017 Jan 1;8(45):78965-78977. https://doi.org/10.18632/oncotarget.20697
Hayashi, Masanori ; Zhu, Peixuan ; McCarty, Gregory ; Meyer, Christian F. ; Pratilas, Christine A. ; Levin, Adam ; Morris, Carol D. ; Albert, Catherine M. ; Jackson, Kyle W. ; Tang, Cha Mei ; Loeb, David M. / Size-based detection of sarcoma circulating tumor cells and cell clusters. In: Oncotarget. 2017 ; Vol. 8, No. 45. pp. 78965-78977.
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