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Chinese Hamster Ovary Cells Expressing α 4 β 1 Integrin Stimulate Osteoclast Formation In Vitro
Author(s) -
Akatsu Takuhiko,
Ono Katsuhiro,
Murakami Takehiko,
Katayama Yasuyuki,
Nishikawa Miyuki,
Wada Seiki,
Yamamoto Michiko,
Kugai Nobuo,
Matsuura Nariaki,
Takada Yoshikazu,
Nagata Naokazu
Publication year - 1998
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1998.13.8.1251
Subject(s) - bone marrow , osteoclast , stromal cell , chinese hamster ovary cell , bone resorption , tartrate resistant acid phosphatase , spleen , prostaglandin e2 , chemistry , microbiology and biotechnology , biology , endocrinology , medicine , cell culture , in vitro , immunology , biochemistry , genetics
It is reported that Chinese hamster ovary cells transfected with human α 4 cDNA (α 4 CHOs) and expressing functional α 4 β 1 integrin developed bone metasasis in nude mice. To clarify the role of α 4 β 1 integrin in bone metastasis, in terms of tumor‐mediated bone destruction, we examined whether α 4 CHOs stimulate osteoclast formation in cocultures with mouse bone marrow cells. The number of osteoclast‐like cells identified as tartrate‐resistant acid phosphatase positive multinucleated cells (TRAP(+) MNCs) formed from bone marrow cells increased with the increasing number of α 4 CHOs cocultured. The effects of 1,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) and prostaglandin E 2 (PGE 2 ) on TRAP(+) MNC formation were enhanced in cocultures with α 4 CHOs. TRAP(+) MNCs induced by α 4 CHOs possessed calcitonin receptors and resorbed calcified tissues. In cocultures, α 4 CHOs and bone marrow stromal cells were in contact with each other and bone marrow stromal cells expressed vascular cell adhesion molecule‐1 (VCAM‐1), which is one of the ligands for α 4 β 1 integrin. TRAP(+) MNC formation was not stimulated in cocultures where direct contact between α 4 CHOs and bone marrow cells was inhibited by membrane filters. α 4 CHOs do not support TRAP(+) MNC formation in cocultures with spleen cells but do support TRAP(+) mononuclear cell and MNC formation from spleen cells in the presence of osteoblastic cells. Cultured media from α 4 CHOs, bone marrow cells, and cocultures of α 4 CHOs and bone marrow cells did not stimulate TRAP(+) MNC formation or enhance the effects of 1,25(OH) 2 D 3 and PGE 2 in bone marrow cultures. The concentrations of PGE 2 and interleukin‐6 (IL‐6) in cultured media were not different between the cultures of bone marrow cells and the cocultures of bone marrow cells and α 4 CHOs. Anti‐human α 4 and anti‐mouse VCAM‐1 antibodies inhibited TRAP(+) MNC formation induced by α 4 CHOs. These results indicate that α 4 CHOs stimulated TRAP(+) MNC formation through direct cell‐to‐cell interaction between α 4 β 1 and VCAM‐1. It is suggested that in addition to various soluble factors regulating osteoclast formation, cell‐to‐cell interaction between tumor cells and bone marrow cells is important for inducing osteoclasts at the site of bone metastasis and leading to bone destruction.