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Revista de Osteoporosis y Metabolismo Mineral

On-line version ISSN 2173-2345Print version ISSN 1889-836X

Abstract

ALVAREZ CARRION, L; GUTIERREZ ROJAS, I; ARDURA, JA  and  ALONSO, V. Osteogenic cells affected by soluble tumor factors contribute to bone pre-metastatic niche formation. Rev Osteoporos Metab Miner [online]. 2019, vol.11, n.2, pp.64-71.  Epub Jan 20, 2020. ISSN 2173-2345.  https://dx.doi.org/10.4321/s1889-836x2019000200005.

Objective:

To analyze the effect of the secrets of solid organotropic tumors towards bone in osteogenic, osteoblastic and osteocytic lineage cells, in the expression of genes related to bone metabolism.

Material and method:

We characterize the changes in gene expression by quantitative real-time PCR of the OPG/RANKL axis, as well as other genes related to osteoblastic differentiation such as Runx2 and osteocalcin, induced by the conditioned means of prostate tumor cells, breast and melanoma in pre MC3T3-E1 osteoblasts and murine MLO-Y4 osteocytes or in human osteoblasts, as appropriate by species.

Results:

Stimulation of osteocitic cells with conditioned means of melanoma or prostate adenocarcinoma cells induced an increase in OPG and RANKL gene expression, with the OPG/RANKL ratio being increased. Only the secretome of prostate adenocarcinoma cells altered the expression of Runx2 in osteocytes. Conditioned media of breast cancer cells only modified the expression of RANKL in osteoblast cells, with a decrease in OPG/RANKL ratio.

Conclusion:

Soluble tumor factors have osteocitic cells as their cellular target, favoring the induction of a pre-metastatic bone niche by modifying the OPG/RANKL ratio in the bone environment, and, thus, the progression of bone organotropic tumors such as melanoma and prostatic adenocarcinomas.

Keywords : bone organotropic tumors; soluble tumor factors; pre-metastatic bone niche; bone metastases; osteocytes and osteoblasts.

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