To further prove that the pro-metastatic effects of SPP1 were mediated through PMN remodeling rather than augmenting the invasiveness of the primary tumor, we generated an N-terminal signal peptide deleted SPP1 mutant in Hepa1-6 (Hepa1-6SPP1△1–48, also known as SPP1 isoform-2), which preserves the intracellular expression and bioactivity of full-length SPP1 while simultaneously inhibiting its extracellular secretion (Figure S2A-B) [31]. The gene discussed is SPP1; the disease is neoplasm.