Interleukin-15 and transforming growth factor alpha are associated with depletion of tumor-associated macrophages in colon cancer.
We examined the effects of IL-15 and TGF-alpha on the inhibition of macrophage infiltration into colon cancer tissue, and secretion of amphoterin from colon cancer cells. Production of IL-15 and/or TGF-alpha was associated with depletion of tumor-associated macrophages (TAMs) in both Dukes' B and C tumors (P = 0.0324 and 0.0051, respectively). Production of IL-15 and/or TGF-alpha was also associated with amphoterin mRNA expression in colon cancer tissues with TAM depletion in both Dukes' B and C tumors (P = 0.0167 and P = 0.0062, respectively). WiDr human colon cancer cells treated with IL-15 and/or TGF-alpha induced reduction of nucleus-localized amphoterin and an increase in cytosolic and membranous amphoterin. Moreover, IL-15 and/or TGF-alpha treatment increased amphoterin secretion by WiDr cells. Most notably, IL-15 and TGF-alpha treatment induced the increase of cytosol/membrane localization and secretion of amphoterin and the most pronounced effect among the treatments carried out. These results suggested that IL-15/TGF-alpha promotes depletion of TAMs and secretion of amphoterin in colon cancer.
Sasahira
T
T
Dept. of Molecular Pathology, Nara Medical University, Kashihara, Nara, Japan.
Sasaki
T
T
Kuniyasu
H
H
D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002452:Cell Count; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000378:metabolism* / Q000494:pharmacology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D024243:HMGB1 Protein; D019409:Interleukin-15; D016211:Transforming Growth Factor alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule