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Isolation and characterization of circulating tumor cells from human gastric cancer patients

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Circulating tumor cells (CTCs) have been proved to be responsible for tumor metastasis and resistant to anticancer therapies. This study aims to isolate and characterize circulating tumor cells from human gastric cancer patients, and investigate characteristic differences between gastric CTCs and gastric cancer cell lines.

Methods

We analyzed 31 cases of gastric cancer patients using anti-CD45 antibody-conjugated magnetic microbeads negative separation, combined with fluorescence activated cell sorter CD44 positive screening. Abilities of tumor formation, metastasis, invasion, migration, irradiation and drug sensitivity of CTCs and gastric cancer cell lines were detected and compared.

Results

Of all the 31 patients, CD44+/CD45−CTCs were isolated in 14 patients, of which 3 cases were stage IIA, 2 cases stage IIB, 2 cases stage IIIC and 7 cases stage IV. The malignant behavior was demonstrated by both clonogenetic assay and tumor xenograft in nude mice. Compared with human gastric cancer cell lines, the migration and invasion abilities of CTCs increased to 3.21–12.6-fold and 2.3–6.7-fold, respectively (all p values <0.05). In addition, the metastatic potential of CTCs is much higher in vivo than that of the control. Furthermore, CTCs were found to be relatively sensitive to FU, cisplatin and paclitaxel, but relatively resistant to irradiation, oxaliplatin, cetuximab and trastuzumab.

Conclusions

CD44+/CD45− gastric CTCs were isolated and found to exhibit stronger malignant behavior when compared with human gastric cancer cell lines. Furthermore, CTCs cultured in vitro have potential implications in drug sensitivity screening for the future anticancer treatments.

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Abbreviations

CTCs:

Circulating tumor cells

FACS:

Fluorescence activated cell sorter

USPIO:

Ultrasmall superparamagnetic iron oxide

EMT:

Epithelial–mesenchymal transition

HER1:

Epidermal growth factor receptor1

HER2:

Epidermal growth factor receptor2

EpCaM:

Epithelial cell adhesion molecule

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Acknowledgments

We greatly appreciate the financial support from the National Basic Research Program of China (973 Program, 2011CB935800) (http://www.973.gov.cn/English/Index.aspx) and the National Natural Science Foundation (30971519) (http://www.nsfc.gov.cn/Portal0/default166.htm). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, 610041, China

    Dandan Yuan, Ming Liu & Feng Bi

  2. Laboratory of Signal Transduction and Molecular Target Therapy, West China Hospital, Sichuan University, Chengdu, 610041, China

    Dandan Yuan, Liang Chen, Mingxing Li, Hongwei Xia, Yuchen Zhang, Qiulin Tang & Feng Bi

  3. Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu, 610041, China

    Tie Chen & Xianming Mo

  4. Laboratory of Molecular Image, West China Hospital, Sichuan University, Chengdu, 610041, China

    Rui Xia & Fabao Gao

Authors
  1. Dandan Yuan
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  2. Liang Chen
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  4. Hongwei Xia
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  11. Ming Liu
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  12. Feng Bi
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Corresponding authors

Correspondence to Ming Liu or Feng Bi.

Electronic supplementary material

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432_2014_1814_MOESM1_ESM.tif

Supplementary material 1 Expression of CD44 in CTCs and gastric cancer cell lines detected by Western blot. CD44 was detected in CTCs and gastric cancer cell lines, and no significance was found between each group. (TIFF 39 kb)

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Yuan, D., Chen, L., Li, M. et al. Isolation and characterization of circulating tumor cells from human gastric cancer patients. J Cancer Res Clin Oncol 141, 647–660 (2015). https://doi.org/10.1007/s00432-014-1814-0

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  • DOI: https://doi.org/10.1007/s00432-014-1814-0

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