{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T03:34:21Z","timestamp":1789356861437,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T00:00:00Z","timestamp":1396483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:p>Bone metastasis is a multistep process that includes cancer cell dissemination, colonization, and metastatic growth. Furthermore, this process involves complex, reciprocal interactions between cancer cells and the bone microenvironment. Bone resorption is known to be involved in both osteolytic and osteoblastic bone metastasis. However, the precise roles of the bone resorption in the multistep process of osteoblastic bone metastasis remain unidentified. In this study, we show that bone resorption plays important roles in cancer cell colonization during the initial stage of osteoblastic bone metastasis. We applied bioluminescence\/X\u2010ray computed tomography multimodal imaging that allows us to spatiotemporally analyze metastasized cancer cells and bone status in osteoblastic bone metastasis models. We found that treatment with receptor activator of factor\u2010\u03baB ligand (<jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>) increased osteoblastic bone metastasis when given at the same time as intracardiac injection of cancer cells, but failed to increase metastasis when given 4\u00a0days after cancer cell injection, suggesting that <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>\u2010induced bone resorption facilitates growth of cancer cells colonized in the bone. We show that insulin\u2010like growth factor\u20101 released from the bone during bone resorption and hypoxia\u2010inducible factor activity in cancer cells cooperatively promoted survival and proliferation of cancer cells in bone marrow. These results suggest a mechanism that bone resorption and hypoxic stress in the bone microenvironment cooperatively play an important role in establishing osteoblastic metastasis.<\/jats:p>","DOI":"10.1111\/cas.12391","type":"journal-article","created":{"date-parts":[[2014,3,5]],"date-time":"2014-03-05T18:50:45Z","timestamp":1394045445000},"page":"553-559","source":"Crossref","is-referenced-by-count":12,"title":["Bone resorption facilitates osteoblastic bone metastatic colonization by cooperation of insulin\u2010like growth factor and hypoxia"],"prefix":"10.1111","volume":"105","author":[{"given":"Takahiro","family":"Kuchimaru","sequence":"first","affiliation":[{"name":"Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Aikawa","sequence":"additional","affiliation":[{"name":"Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisataka","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Planning and Development Bioindustry Division Oriental Yeast Co. 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