Galectin-3 Cleavage Alters Bone Remodeling: Different Outcomes in Breast and Prostate Cancer Skeletal Metastasis

Cancer Research
Kosei NakajimaAvraham Raz

Abstract

Management of bone metastasis remains clinically challenging and requires the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Galectin-3 (Gal-3) has been implicated as a secreted factor that alters the bone microenvironment. Proteolytic cleavage of Gal-3 may also contribute to malignant cellular behaviors, but has not been addressed in cancer metastasis. Here, we report that Gal-3 modulates the osteolytic bone tumor microenvironment in the presence of RANKL. Gal-3 was localized on the osteoclast cell surface, and its suppression by RNAi or a specific antagonist markedly inhibited osteoclast differentiation markers, including tartrate-resistant acid phosphatase, and reduced the number of mature osteoclasts. Structurally, the 158-175 amino acid sequence in the carbohydrate recognition domain (CRD) of Gal-3 was responsible for augmented osteoclastogenesis. During osteoclast maturation, Gal-3 interacted and colocalized with myosin-2A along the surface of cell-cell fusion. Pathologically, bone metastatic cancers expressed and released an intact form of Gal-3, mainly detected in breast cancer bone metastases, as well as a cleaved form, more abundant in prostate cancer bone m...Continue Reading

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Citations

Apr 14, 2016·Cancer Metastasis Reviews·Kosei NakajimaAvraham Raz
Dec 30, 2016·Allergy·E Jensen-JarolimS N Karagiannis
Jan 10, 2018·Glycobiology·Pratima Nangia-MakkerAvraham Raz
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Mar 22, 2019·International Journal of Molecular Sciences·Emma Scott, Jennifer Munkley
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Jun 24, 2018·Cellular and Molecular Life Sciences : CMLS·Daniela WeinmannHans-Joachim Gabius
Nov 21, 2019·Calcified Tissue International·Kevin A MaupinBart O Williams
Sep 16, 2020·Cancer Metastasis Reviews·Kosei NakajimaAvraham Raz
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Oct 10, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Kosei NakajimaHiromasa Miura
Feb 19, 2021·The Biochemical Journal·Ramiro M PerrottaGabriel A Rabinovich
Oct 27, 2020·Journal of Bone Oncology·Kosei Nakajima, Avraham Raz
Apr 6, 2021·Frontiers in Pharmacology·Milica VelickovicNebojsa Arsenijevic

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