Recruitment of Circulating Breast Cancer Cells Is Stimulated by Radiotherapy

• Radiation of tumor cells in vitro and in vivo attracts migrating tumor cells
• Expression of GM-CSF is stimulated by radiation
• GM-CSF is required for radiation-induced tumor reseeding

SummaryRadiotherapy (RT) is a localized therapy that is highly effective in killing primary tumor cells located within the field of the radiation beam. We present evidence that irradiation of breast tumors can attract migrating breast cancer cells. Granulocyte-macrophage colony stimulating factor (GM-CSF) produced by tumor cells in response to radiation stimulates the recruitment of migrating tumor cells to irradiated tumors, suggesting a mechanism of tumor recurrence after radiation facilitated by transit of unirradiated, viable circulating tumor cells to irradiated tumors. Data supporting this hypothesis are presented through in vitro invasion assays and in vivo orthotopic models of breast cancer. Our work provides a mechanism for tumor recurrence in which RT attracts cells outside the radiation field to migrate to the site of treatment.

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