We detect tumour cell fusion in vivo on mouse model.
Chemotherapy promotes tumour cell hybridization in vivo.
Spontaneous cell-cell fusion has been recognized to be an important mechanism for tissue and organ development and repair. In cancer, cell fusion is critically involved in tumourigenesis, metastasis and drug resistance, as illustrated by in vitro experiments. However, there has been no direct detection of tumour cell fusion or hybridization in an in vivo tumour environment, and the features of hybridized cells under selective pressures, such as chemotherapy, are unknown. Here, we expressed two fluorescent marker proteins in the human breast cancer cell line SKBR3 to detect tumour cell hybridization in vivo and performed a xenograft chemotherapy experiment in mice to evaluate the chemotherapeutic response of the hybrids. The mice treated by epirubicin showed that chemotherapy promoted tumour cell hybridization in vivo, which elicited the production of more hybrids in the outer section of the tumour. These results provide the first in vivo evidence of tumour cell fusion and indicate that chemotherapy may contribute to a poor prognosis by enriching for fused cells, which are more malignant. It is therefore necessary to reassess chemotherapy strategies.
Figure S1 Control gates for FACS. a. Gate B: SKBR3 cells expressing no fluorescent proteins (negative control gate). b. Gate C: SKBR3 cells only expressing EGFP (EGFP control gate). c. Gate A: SKBR3 cells only expressing mCherry (mCherry control gate). d. Gate P: SKBR3 cells expressing both EGFP and mCherry in each cell (positive control gate). e. A mixture of SKBR3 cells expressing no fluorescent protein, EGFP or mCherry. These data were used to calculate the false positive rate. f. A mixture of SKBR3 cells expressing no fluorescent protein, EGFP, mCherry or both EGFP and mCherry. These data were used to calculate the discrimination ability of FACS. (PDF 1136 kb)13277_2015_4337_MOESM1_ESM.pdf
Table S1 (PDF 64 kb)13277_2015_4337_MOESM2_ESM.pdf
Aichel O. Über Zellverschmelzung mit qualitativ abnormer Chromosomenverteilung als Ursache der Geschwulstbildung. vol 13. W. Engelmann; 1911.
Miller FR, Mohamed AN, McEachern D. Production of a more aggressive tumor cell variant by spontaneous fusion of two mouse tumor subpopulations. Cancer Res. 1989;49(15):4316–21. PubMed
Naito S, Von Eschenbach AC, Giavazzi R, Fidler IJ. Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res. 1986;46(8):4109–15. PubMed
Lu X, Kang Y. Cell fusion hypothesis of the cancer stem cell. Cell Fusion in Health and Disease. Springer; 2011. p. 129–40.
- Chemotherapy promotes tumour cell hybridization in vivo
- Springer Netherlands