Depletion of tumor-infiltrating macrophages is associated with amphoterin expression in colon cancer

Abstract

Macrophage infiltration into colon cancer and amphoterin expression in cancer cells was examined in 42 human colon cancers invading the subserosa. The mean number of infiltrating macrophages was significantly higher in Dukes' B cases than in Dukes' C cases (p = 0.0065). Tumors with few infiltrating macrophages (macrophage depletion) were significantly more frequent in Dukes' C cases than in Dukes' B cases (p = 0.0014). No Dukes' C cases with relevant macrophage infiltration showed macrophage-cancer cell contact, whereas 5 Dukes' B cases showed such contact (p < 0.0001). In human colon cancer cells implanted in the cecum of nude mice, KM12SM (highly metastatic) tumors yielded less macrophage infiltration and more liver metastases than KM12C (low risk of metastasis) tumors (14 +/- 3 vs. 78 +/- 32 and 24 +/- 6 vs. 5 +/- 3 per liver, respectively). Amphoterin expression was detected at high frequency in both Dukes' B and C cases (p = 0.0684). In macrophage-depleted cases, amphoterin expression was significantly higher than that in non-depleted cases (p = 0.0015). To confirm biological effects of amphoterin on macrophages, an infiltration assay using the cell-layered Boyden chamber was done. Infiltration of PMA-treated U937 monocytes through the KM12SM cell layer was increased by pretreatment of KM12SM cells with amphoterin antisense S-oligodeoxynucleotide exposure. Moreover, extracted amphoterin inhibited PMA-U937 monocyte infiltration in a dose-dependent manner. Thus, amphoterin may play an important role in the inhibition of macrophage infiltration into colon cancer.