Establishment of patient-derived tumor spheroids for non-small cell lung cancer

PLoS One. 2018 Mar 15;13(3):e0194016. doi: 10.1371/journal.pone.0194016. eCollection 2018.

Abstract

The prognosis of advanced non-small cell lung cancer (NSCLC) patients is poor. One of the reasons for this hampered progress has been a lack of in vitro models that would faithfully recapitulate the heterogeneity of tumors and response to treatment. In this study, surgically resected tumors were obtained from patients with stage I/II NSCLC during curative-intent surgery. Using a 3D patient-derived tumor spheroids culture system, our results demonstrate successful long-term expansion of primary NSCLC cells in vitro (> 120 days). Patient-derived tumor spheroid (PDS) cultures could be established with a success rate of 100% (3 out of 3 samples). Consistent with their growth in culture and their cancer type, many cells within the tumor spheroids were stained positive for Ki67 and thyroid transcription factor-1. The result of this study supports the establishment of an expandable 3D in vitro NSCLC model for drug screening, and enables the potential long term studies such as the establishment of drug resistant models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Culture Techniques / methods
  • Cell Line, Tumor
  • Humans
  • Ki-67 Antigen / metabolism
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology*
  • Thyroid Nuclear Factor 1 / metabolism

Substances

  • Ki-67 Antigen
  • Thyroid Nuclear Factor 1

Grant support

This work was supported by the Second Affiliated Hospital of Soochow University Preponderant Clinic Discipline Group Project Funding (XKQ2015OO5) and the Suzhou Municipal Key Medical Disciplines (Respiratory Medicine) grant (SZXK201506). This work was also funded in part by Invitrocue Biomedical Service Suzhou. The funders provided support in the form of salaries for authors [Z.Z., H.W., Q.D., Y.X., Z.X., C.L., D.L., L.X., W.X., C.Z. and M.S.], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.