We show that either prior PDIA3 inhibition by the disulfide isomerase inhibitor 16F16 or depletion of heparin-binding proteins strongly reduces the activity of conditioned medium (CM) of MDA-MB-231 human breast cancer cells to support promigratory cell spreading and F-actin organization by newly adherent MDA-MB-231 cells. Here, PDIA3 is linked to breast cancer.