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Interleukin‐6 produced by pancreatic carcinoma cells enhances humoral immune responses against tumor cells: A possible event in tumor regression
Author(s) -
Saito Katsunori,
Ishikura Hiroshi,
Kishimoto Takashi,
Kawarada You,
Yano Tomoyuki,
Takahashi Toshiyuki,
Kato Hiroyuki,
Yoshiki Takashi
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980119)75:2<284::aid-ijc18>3.0.co;2-d
Subject(s) - conventional pci , cytokine , metastasis , cancer research , immune system , antibody , biology , clone (java method) , carcinoma , medicine , immunology , cancer , dna , genetics , myocardial infarction
Production of interleukin‐6 (IL‐6) by human pancreatic carcinoma cells inversely correlates with potentials for blood‐borne metastasis to the liver in nude mice. IL‐6 cDNA was transfected to PCI‐43, one of our cultured pancreatic carcinoma cell lines that does not produce IL‐6 and generates numerous metastases to the liver. An IL‐6 high‐producer clone (PCI‐43h) generated few metastases; IL‐6 production thus has a direct effect on metastasis, whereas other transfectants (PCI‐43I and PCI‐43n), which are IL‐6 low‐, and IL‐6 non‐producers, respectively, did generate metastases. Tumor‐reactive IgG, which mediated antibody‐dependent cellular cytotoxicity (ADCC) in vitro, was detected in sera from recipient nude mice inoculated with PCI‐43h but not in sera from mice given PCI‐43I, PCI‐43n or parent PCI‐43. Tumor‐reactive IgM was detected in sera from all mice, irrespective of inoculated PCI‐43 species, with a slight augmentation being noted in PCI‐43h‐inoculated nude mice. Severe combined immunodeficiency (SCID) beige mice were then used as recipients for PCI‐43 species, and tumorigeneity was examined by s.c. inoculation of a suboptimal number of PCI‐43 transfectants (1 × 10 6 /0.1 ml). Only PCI‐43h formed palpable masses in SCID beige mice, whereas it first grew to be palpable but subsequently became not palpable in nude mice, thereby revealing a dual action of tumor‐derived IL‐6. Thus, tumor‐derived IL‐6 confers growth promotion in SCID beige mice, while the same cytokine exhibits anti‐tumorigenic functions, presumably through humoral immune responses, in nude mice. Int. J. Cancer 75:284–289, 1998. © 1998 Wiley‐Liss, Inc.