The propensity of invasive circulating tumor cells (iCTCs) in metastatic progression and therapeutic responsiveness.
Cancer Med
; 8(8): 3864-3874, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31115187
ABSTRACT
Circulating tumor cells (CTCs) are important clinical indicators of metastatic progression and treatment efficacy. However, because of their low number and heterogeneity, reliable patient-derived CTC models are not readily available. We report here the isolation and characterization of the invasive population of CTCs, iCTCs, from blood of 10 patients with epithelial ovarian cancer (EOC) and one pancreatic cancer patient based on the avidity of tumor cells toward an artificial collagen-based adhesion matrix (CAM), in comparison with tumor progenitor (TP) cells isolated from tumor cell lines, tumors and ascites from EOC patients. CAM-avid cells identified to be iCTCs were indistinguishable with TP cells using either functional CAM uptake or surface markers (seprase and CD44). In addition, iCTCs were characterized using peritoneal and spontaneous metastasis models in vivo to evaluate their metastatic propensity and therapeutic response. TP cells and iCTCs had a doubling time of about 34-42 hours. TP cells were rare (<3.5%) in most patient-derived specimens, however, iCTCs emigrated into blood, at a high frequency, 64.2% (n = 49). Approximately 500 patient-derived iCTCs recapitulated formation of iCTCs in mouse blood and formed micrometastases in the liver and/or lung, a degree of metastatic spread equivalent to the inoculation of 5 × 105 bulk tumor cells isolated from ascites and tumors. iCTCs were shown to be novel therapeutic targets for blocking metastasis using the reduced formation of iCTCs and micrometastases by RNAi, peptides, and monoclonal antibodies against seprase.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Neoplásicas Circulantes
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article