Morphological quantification of proliferation-to-invasion transition in tumor spheroids.

Yi He, Ling Xiong, Xuejuan Gao, Miaomiao Hai, Yanping Liu, Gao Wang, Guo Chen, Jianwei Shuai, Yang Jiao, Xixiang Zhang, Ruchuan Liu, Liyu Liu

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


BACKGROUND:Metastasis determines the lethality of cancer. In most clinical cases, patients are able to live with tumor proliferation before metastasis. Thus, the transition from tumor proliferation to metastasis/invasion is essential. However, the mechanism is still unclear and especially, the proliferation-to-metastasis/invasion transition point has not been well defined. Therefore, quantitative characterization of this transition is urgently needed. METHODS:We have successfully developed a home-built living-cell incubation system combined with an inverted optical microscope, and a systematic, quantitative approach to describing the major characteristic morphological parameters for the identification of the critical transition points for tumor-cell spheroids in a collagen fiber scaffold. RESULTS:The system focuses on in vitro tumor modeling, e.g. the development of tumor-cell spheroids in a collagen fiber scaffold and the monitoring of cell transition from proliferation to invasion. By applying this approach to multiple tumor spheroid models, such as U87 (glioma tumor), H1299 (lung cancer), and MDA-MB-231 (breast cancer) cells, we have obtained quantitative morphological references to evaluate the proliferation-to-invasion transition time, as well as differentiating the invasion potential of tumor cells upon environmental changes, i.e. drug application. CONCLUSIONS:Our quantitative approach provides a feasible clarification for the proliferation-to-invasion transition of in vitro tumor models (spheroids). Moreover, the transition time is a useful reference for the invasive potential of tumor cells. GENERAL SIGNIFICANCE:This quantitative approach is potentially applicable to primary tumor cells, and thus has potential applications in the fields of cancer metastasis investigations and clinical diagnostics.
Original languageEnglish (US)
Pages (from-to)129460
JournalBiochimica et biophysica acta. General subjects
Issue number1
StatePublished - Nov 2 2019

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: This work was supported by the National Natural Science Foundation of China (Grant Nos. 11674043 and 11604030), the Fundamental Research Funds for the Central Universities (2018CDJDWL0011), and the Fundamental and Advanced Research Program of Chongqing (Grant #cstc2018jcyjAX0338), China. We have no conflict of interest.


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