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Effect of IL‐1 on experimental bone/bone‐marrow metastases
Author(s) -
Arguello Francisco,
Baggs Raymond B.,
Graves Brian T.,
Harwell Shari E.,
Cohen Harvey J.,
Frantz Christopher N.
Publication year - 1992
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/ijc.2910520522
Subject(s) - bone marrow , medicine , stromal cell , metastasis , bone metastasis , haematopoiesis , endocrinology , cancer , pathology , cancer research , biology , stem cell , genetics
Bone metastasis is a common event and a major cause of morbidity in cancer patients. The hematopoietic marrow of the bones, rather than the bone tissue per se, is the target organ in bone metastasis. In the bone marrow, IL‐1 induces the release of hematopoietic growth factors that may affect tumor‐cell growth. We treated groups of mice with rhulL‐1α to examine its role in the establishment of experimental bone/bone‐marrow metastasis. We found that injection of 2 μg of rhulL‐1α 24 hr prior to, simultaneously with or 24 hr after the injection of 10 4 B16 melanoma cells into the left cardiac ventricle of mice resulted in a 2‐fold increase in the average number of colonized bones per mouse. GM‐CSF is produced by bone‐marrow stromal cells in response to IL‐1, and its receptor has been found on tumor cells, including melanoma cells. However, the administration of rmu GM‐CSF to mice by either multiple injections or continuous infusion did not affect the number of colonized bones. Many of the biologic effects of IL‐1 are mediated by prostaglandins. Treatment of mice with 100 μg of indomethacin, a potent inhibitor of prostaglandin synthesis, prior to the injection of rhulL‐ 1α, prevented the increase in number of bone metastases. To determine whether constitutive productions of IL‐1 and/or prostaglandins are involved in the pathogenesis of bone/bone marrow metastasis, we treated mice with antimouse IL‐1α neutralizing antibodies, rhulRAP (an inhibitor of IL‐1 activity) or indomethacin. We found no difference in the average number of colonized bones per mouse between treated and control mice. We conclude that exogenous administration of IL‐1 enhances experimental bone/bone‐marrow metastases, and that this phenomenon is mediated through prostaglandins. However, neither the constitutive production of IL‐1 nor that of prostaglandins appear to play a role in the pathogenesis of bone/bone‐marrow metastasis in our murine model system. © 1992 Wiley‐Liss, Inc.