(1) EphA4‐deleted microenvironment reduced tumor growth and metastasis mainly via reduction in an IGF1 synthesis signal; (2) An excess of IGF1 supply over demand to the control mice could not further accelerate the tumor development; (3) The cancer‐associated leukemoid reaction is far from incidental epiphenomenon, secondary to underlying primary disease and the severe leukemoid reaction is lethal; (4) Targeting host EphA4 expression may serve as a novel candidate in blocking the tumor progression vicious circle (Fig. 6E) for G‐CSF‐releasing or IGF1‐dependent cancer. Here, CSF3 is linked to neoplasm.