Parathyroid hormone-related protein (PTHrP) is responsible for production of bone metastasis, but not visceral metastasis, by human small cell lung cancer SBC-5 cells in natural killer cell-depleted SCID mice.
We previously established an osteolytic bone metastasis model with multiorgan dissemination in natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice using human small cell lung cancer cells (SBC-5), which highly express the parathyroid hormone-related protein (PTHrP). In our present study, we evaluated the role of PTHrP on bone metastasis by SBC-5 cells using anti-PTHrP neutralizing antibody (Ab). Anti-PTHrP Ab did not affect the proliferation or cytokine production of SBC-5 cells in vitro. Repeated intravenous injection with anti-PTHrP Ab inhibited the formation of bone metastasis in a dose-dependent manner, while the same treatment had no significant effect on the metastasis to visceral organs (lung, liver, kidney and lymph node). In addition, treatment with anti-PTHrP Ab improved the elevated serum calcium level, associated with inhibition of osteolytic bone metastasis, suggesting that anti-PTHrP Ab inhibited bone metastasis via suppression of bone resorption probably by neutralizing PTHrP. These findings suggest that PTHrP is essential for bone metastasis, but not visceral metastasis, by small cell lung cancer SBC-5 cells.
Miki
Toyokazu
T
Department of Internal Medicine and Molecular Therapeutics, Course of Bioregulation and Medical Oncology, University of Tokushima School of Medicine, Tokushima, Japan.
Yano
Seiji
S
Hanibuchi
Masaki
M
Kanematsu
Takanori
T
Muguruma
Hiroaki
H
Sone
Saburo
S
D000818:Animals; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000556:secondary*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000556:secondary; D007694:Killer Cells, Natural / Q000502:physiology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology*; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016207:Cytokines; D044162:Parathyroid Hormone-Related Protein; D002118:Calcium