Premium
Mechanism for bone invasion of oral cancer cells mediated by interleukin‐6 in vitro and in vivo
Author(s) -
Okamoto Masato,
Hiura Kenji,
Ohe Go,
Ohba Yasuo,
Terai Kunihoro,
Oshikawa Tetsuya,
Furuichi Sachiko,
Nishikawa Hidetomo,
Moriyama Keiji,
Yoshida Hideo,
Sato Mitsunobu
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20001101)89:9<1966::aid-cncr13>3.0.co;2-r
Subject(s) - bone resorption , medicine , chemotaxis , in vivo , antibody , cancer , in vitro , cancer cell , cancer research , cell culture , immunology , pathology , chemistry , biology , receptor , biochemistry , microbiology and biotechnology , genetics
BACKGROUND Osteoclastic bone resorption is an important step in bone invasion in several malignancies. Although interleukin (IL)‐6 accelerates osteoclastic bone resorption, it remains unclear whether IL‐6 may be involved in bone invasion of oral cancer. METHODS The pit formation assay with calf femur‐derived bone slices was performed to examine the bone‐resorbing activity of osteoclasts and cancer cells. The chemotaxis activity of the culture media was analyzed by the use of Boyden chamber technique. Nude mice, which were inoculated with IL‐6–producing oral cancer cells into masseter, were treated with anti–IL‐6 neutralizing antibody, and mandibular‐bone invasion of the cells was assessed. RESULTS BHY, a bone‐invasive oral cancer cell line, but not HNT, a noninvasive cell line, produced large amounts of IL‐6. In a pit formation assay, addition of conditioned medium (CM) derived from BHY but not HNT increased osteoclastic bone resorption, and the effects were inhibited by anti–IL‐6 antibody. BHY‐secreted IL‐6 showed significant chemotaxis activity for osteoclasts. Of note, CM from the cocultivation of osteoclasts and BHY markedly enhanced the cancer cell migration, and the chemotaxis activity was significantly reduced when anti–IL‐6 antibody was added into the coculture and then CM were collected, but not when the antibody was added into the CM after they were collected. Furthermore, treatment with anti–IL‐6 antibody almost completely inhibited mandibular bone invasion of BHY in nude mice. CONCLUSIONS These results strongly suggest that IL‐6 secreted by oral cancer cells plays a significant role in bone invasion. Cancer 2000;89:1966–75. © 2000 American Cancer Society.