Intratumoral genetic heterogeneity is a feature of head and neck squamous cell carcinomas (HNSCCs) and correlates with poor clinical outcome. We have developed in vitro and in vivo models with which to investigate the genetic basis for the development and maintenance of multiclonality of HNSCCs and the contribution that it makes to tumor growth and treatment.
We show, using intravital lineage tracing in experimental tumours in Confetti mice, that HNSCCs are frequently multiclonal, being derived from neighbouring clones of normal keratinocytes. We also demonstrate, using in vitro and in vivo assays, that genetically and phenotypically distinct populations of HNSCC cells can interact symbiotically to increase growth, motility and invasion. These observations suggest that intratumoral heterogeneity can be more than just a consequence of genetic instability, but actually drive cancer progression by producing clones that have complementary phenotypes.