Together, the results from the above experiments involving multiple approaches to evaluate the role of non-tumorigenic clones and AREG in regulating CL31 metastasis provide strong evidence that transient and non-tumorigenic clones cooperate with CL31 to affect tumor aggressiveness and that the interclonal cooperation is, at least in part, dependent on AREG. The gene discussed is AREG; the disease is neoplasm.