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

Zengli Zhang; Huiqian Wang; Qifeng Ding; Yufei Xing; Zhonghua Xu; Chun Lu; Dongdong Luo; Longjiang Xu; Wei Xia; Caicun Zhou; Minhua Shi

doi:10.1371/journal.pone.0194016

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.

Authors

Zengli Zhang¹, Huiqian Wang², Qifeng Ding³, Yufei Xing¹, Zhonghua Xu³, Chun Lu², Dongdong Luo², Longjiang Xu⁴, Wei Xia⁴, Caicun Zhou⁵, Minhua Shi¹

Affiliations

¹ Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, P.R. China.
² Invitrocue Biomedical Service Suzhou, Suzhou, P.R. China.
³ Department of Thoracic & Cardiac Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, P.R. China.
⁴ Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, P.R. China.
⁵ Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, P.R. China.

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

Grants and funding

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.