The benign transformation tendency of malignant tumor cells for intrauterine transplantation.

To the Editor: Troeger et al. [1] have reported that similar early homing of allogeneic and xenogeneic stem cells and reasonable early engraftment of allogeneic murine foetal liver cells (17.1% donor cells in peripheral blood 4 weeks after intrauterine transplantation [IUT]), whereas xenogeneic HSC are rapidly diminished due to non-self-renewal and low differentiation capacities in the host’s microenvironment. IUT, as a promising treatment for foetal defects, is concerned with the rapid growth and immature immune system of the foetus, which may provide an opportunity for engraftment expansion of foreign tissues chiefly including some stem cells [2] such as haematopoietic stem cells (HSCs), embryo stem cells (ESCs) and MSCs. Nevertheless, there are potential hurdles to be overcome in IUT of stem cells, the first being the risk of uncontrolled proliferation and malignant transformation [3]. Striking parallels can be found between stem cells and cancer cells: similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include cancer stem cells – rare cells with indefinite potential for self-renewal which drive tumorigenesis [4]. However, cancer stem cells may display some similarity and distinctive features compared with HSCs, ESCs and MSCs. To explore what happens when malignant tumour cells introduced into the mouse embryo environment at D14D16 by IUT, Astigiano et al. [5] and our primary research demonstrated that the malignant cells, including some embryonic cancer (EC) cells, H22 and S180 cells (the H22 cell line was originated from hepatoma, the S180 cell line from sarcoma) were not capable of causing tumours, remained latent and could be tracked down in tissues during adulthood as benign cells as is the fate of normal stem cells. Further, the malignant tumour cells for IUT showed a differentiation trend to benign cells, fluorescence analysis revealing that expression of protein kinase C (PKC) was markedly reduced in the H22 cells transplanted into the mouse foetal abdominal cavity by IUT after injection at 24h, 48h, and 72h of GFP-expressing H22 cells and laser confocal microscopy analysis in our research. Recent investigation of malignant tumour cells for IUT has shown that there is benign transformation of the malignant phenotype of tumour cells, including proliferation and differentiation. This suggests we may be able to allay concerns about the risk of uncontrolled proliferation and malignant transformation of stem cells through IUT. At the same time it has provided us with new clues, i.e. firstly there were similar and contrary fates as between benign stem cells and malignant stem cells; secondly it indicates that the embryonic environment retains a certain ability to “normalise” tumour cells during post-implantation development as well. Overall, further study of benign and malignant stem cells for IUT may provide insightful information about the obstacles facing IUT, lay the foundations for further understanding of IUT and suggest a new approach to benign transformation of malignant tumour cells.