One mechanism that might explain why tumours maintain intratumoural heterogeneity is that subpopulations of tumour cells cooperate and are all required to maintain tumours. Zhang et al.have identified two different tumour cell populations (mesenchymal-like cells (MLCs) and tumour-initiating cells (TICs)) in a p53-null mouse model of breast cancer that crosstalk with each other to promote tumour growth. Knockdown of WNT2 or CXCL12 ligands in the MLCs or knockdown of their corresponding receptors in the TICs reduced TIC mammosphere formation in co-culture with MLCs. Furthermore, knockdown of WNT2 in the MLCs increased tumour latency in the mice.
References
Zhang, M. et al. Intratumoral heterogeneity in a p53 null mouse model of human breast cancer. Cancer Discov. http://dx.doi.org/10.1158/2159-8290.CD-14-1101 (2015)
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Seton-Rogers, S. Cooperative crosstalk. Nat Rev Cancer 15, 198 (2015). https://doi.org/10.1038/nrc3937
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DOI: https://doi.org/10.1038/nrc3937