ArticleBiochemical and biophysical research communications2019
Lung tumor cells inhibit bone mineralization and osteoblast activity.
Article in Biochemical and biophysical research communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Bone Loss, Osteoporosis, and Skeletal Fragility: Hidden Consequences of Cancer Cachexia.Cells · 2026Review
- From bone to beyond: osteoclasts dictate metastatic fate in lung adenocarcinoma via the OLFML3-DPPA2 stemness switch.Biology direct · 2026Article
- Bone mineral density as an individual prognostic biomarker in NSCLC patients treated with immune checkpoint inhibitors.Frontiers in immunology · 2024Article
- Role of the Osteocyte in Musculoskeletal Disease.Current osteoporosis reports · 2023Review
- Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy.Nutrition & metabolism · 2022Article
- Selection of lncRNAs That Influence the Prognosis of Osteosarcoma Based on Copy Number Variation Data.Journal of oncology · 2022Article
- Osteocytes and Cancer.Current osteoporosis reports · 2021Review
- Non-bone metastatic cancers promote osteocyte-induced bone destruction.Cancer letters · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Patients with non-small cell lung cancer (NSLC) often develop skeletal complications and fractures. To understand mechanisms of bone loss, we developed a murine model of non-metastatic NSLC. Decreased bone mineral density, trabecular thickness and mineralization, without an increase in bone resorption, were observed in vivo in mice injected with Lewis lung adenocarcinoma (LLC1) cells in the absence of tumor cell metastases. A decrease in trabecular bone mineral density was observed in mice injected with cell-free LLC1 CM. Plasma osteoblast biomarkers and PTH-related peptide (PTHrP) were reduced, and parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, calcium and phosphate concentrations were normal in tumor-bearing mice. LLC1 cell conditioned medium (CM) inhibited alkaline phosphatase activity, osteoblast mineralization, and expression of Alpl and Ocn/Bglap mRNA in MC3T3 osteoblast cultures, whereas non-CM or CM from NIH/3T3 fibroblasts did not induce similar changes. LLC1 CM reduced Wnt3a-stimulated Tcf/Lef reporter plasmid activity and Wnt5A, Tcf1 and Lef1 mRNA expression in MC3T3 cells. Although concentrations of the Wnt inhibitor, DKK2, were increased in LLC1 CM compared to non-CM, depletion of DKK2 from LLC1 CM did not completely restore Wnt3a activity in MC3T3 cultures, and recombinant DKK2 failed to inhibit osteoblast mineralization. The data indicate that in a model of lung adenocarcinoma without bone metastases, tumor cells elaborate a secreted factor(s) that reduces bone mass, bone formation and osteoblast Wnt signaling without increases in bone resorption or calcium-regulating hormone concentrations. The factor(s) mediating this inhibition of osteoblast mineralization require further characterization.
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